George DeForest Barnett Professor in Medicine and Professor of Health Research and Policy (Epidemiology)

Medicine - Infectious Diseases

Bio

Bio

Dr. Parsonnet specializes in adult infectious diseases. She has a particular interest in gastrointestinal infections, including H. pylori infection and diarrheal diseases, tuberculosis and illnesses with prolonged fever. Dr. Parsonnet also has an active research enterprise in which she studies the way infections contribute to the development of chronic diseases including cancer, allergy and obesity. She has had continuous funding from the National Institutes of Health for over 25 years and has served as a member of numerous advisory boards, professional societies, and scientific review committees.

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Research & Scholarship

Current Research and Scholarly Interests

Our current research includes studies on:

1. The frequency and sequence of symptomatic and asymptomatic microbial exposures in children and their role in determining long-term health (the STORK study). To do this, we are conducting a birth cohort study of 200 children, starting when the children are still in utero. We get weekly information about their health status and also have a huge database of biosamples. We are working with numerous collaborators to look at microbiome, virome and immunome development and their health consequences. Many

2. The effects of antimicrobial chemicals in personal care products on infection, inflammation, endocrine function and the microbiome. We are particularly focused on triclosan and triclocarban, two very common antimicrobial chemicals in toothpaste, soaps and plastics.

3. The uses of probiotics in the US and overseas. We are assessing trends in how probiotics are used by both the public and physicians in the US. We also are investigating whether probiotics can improve nutritional status of babies in the developing world.

4. The effects of the gut microbiome on ability to lose weight when on an intensive diet regimen. This work is being done in conjunction with Dr. Christopher Gardner here at Stanford.

Other research interests include tuberculosis diagnostics and epidemiology and long-term outcomes of H. pylori infection.

Clinical Trials

Triclosan, Triclocarban, and the MicrobiotaRecruiting

Triclosan (5-chloro-2 (22,4-dichlorophenoxy)phenol) is a broad-spectrum antibacterial and
antifungal agent that is found in thousands of common household products, including
deodorants, toothpaste, "antibacterial" soaps, cleaning products, kitchen utensils, bedding,
socks, trash bags. The benefits of triclosan have not been proven except in reducing plaque
and gingivitis when used in toothpaste. In this study, the investigators intend to look at
whether exposure to triclosan changes the colonizing flora of the skin, gut and mouth as well
as changes in certain blood hormone levels, including adipocytokines, androgens, and
inflammatory markers. Changes in the gut microbiota have been associated with a variety of
disease states such as inflammatory bowel disease, colorectal cancer. Additionally,
reductions in the microbiome diversity have been associated with obesity.

The investigators intend to investigate whether the rise in childhood obesity is caused by
the loss of recurrent and chronic infections in modern, industrialized society, beginning in
utero and extending through early childhood. The investigators will also examine whether the
antimicrobial triclosan, present in numerous cleaning and hygiene products, decreases the
incidence of infection within a household.

Stanford is currently not accepting patients for this trial.For more information, please contact Luz Sanchez, 650-724-4947.

Abstract

Commonly prescribed antibiotics are known to alter human microbiota. We hypothesized that triclosan and triclocarban, components of many household and personal care products (HPCPs), may alter the oral and gut microbiota, with potential consequences for metabolic function and weight. In a double-blind, randomized, crossover study, participants were given triclosan- and triclocarban (TCS)-containing or non-triclosan/triclocarban (nTCS)-containing HPCPs for 4 months and then switched to the other products for an additional 4 months. Blood, stool, gingival plaque, and urine samples and weight data were obtained at baseline and at regular intervals throughout the study period. Blood samples were analyzed for metabolic and endocrine markers and urine samples for triclosan. The microbiome in stool and oral samples was then analyzed. Although there was a significant difference in the amount of triclosan in the urine between the TCS and nTCS phases, no differences were found in microbiome composition, metabolic or endocrine markers, or weight. Though this study was limited by the small sample size and imprecise administration of HPCPs, triclosan at physiologic levels from exposure to HPCPs does not appear to have a significant or important impact on human oral or gut microbiome structure or on a panel of metabolic markers. IMPORTANCE Triclosan and triclocarban are commonly used commercial microbicides found in toothpastes and soaps. It is unknown what effects these chemicals have on the human microbiome or on endocrine function. From this randomized crossover study, it appears that routine personal care use of triclosan and triclocarban neither exerts a major influence on microbial communities in the gut and mouth nor alters markers of endocrine function in humans.

Abstract

Antibiotics increase weight in farm animals and may cause weight gain in humans. We used electronic health records from a large primary care organization to determine the effect of antibiotics on weight and BMI in healthy adolescents with acne.We performed a retrospective cohort study of adolescents with acne prescribed ?4 weeks of oral antibiotics with weight measurements within 18 months pre-antibiotics and 12 months post-antibiotics. We compared within-individual changes in weight-for-age Z-scores (WAZs) and BMI-for-age Z-scores (BMIZs). We used: (i) paired t-tests to analyse changes between the last pre-antibiotics versus the first post-antibiotic measurements; (ii) piecewise-constant-mixed models to capture changes between mean measurements pre- versus post-antibiotics; (iii) piecewise-linear-mixed models to capture changes in trajectory slopes pre- versus post-antibiotics; and (iv) ?(2) tests to compare proportions of adolescents with ?0.2 Z-scores WAZ or BMIZ increase or decrease.Our cohort included 1012 adolescents with WAZs; 542 also had BMIZs. WAZs decreased post-antibiotics in all analyses [change between last WAZ pre-antibiotics versus first WAZ post-antibiotics?=?-0.041 Z-scores (P?0.001); change between mean WAZ pre- versus post-antibiotics?=?-0.050 Z-scores (P?0.001); change in WAZ trajectory slopes pre- versus post-antibiotics?=?-0.025 Z-scores/6 months (P?=?0.002)]. More adolescents had a WAZ decrease post-antibiotics ?0.2 Z-scores than an increase (26% versus 18%; P?0.001). Trends were similar, though not statistically significant, for BMIZ changes.Contrary to original expectations, long-term antibiotic use in healthy adolescents with acne was not associated with weight gain. This finding, which was consistent across all analyses, does not support a weight-promoting effect of antibiotics in adolescents.

Abstract

Stanford's Outcomes Research in Kids (STORK) is an ongoing prospective cohort of healthy pregnant women and their babies established to determine the effect of infectious diseases on weight, linear growth and immune system development during childhood. Additionally, a nested randomised intervention of household and personal cleaning products tests the effects of the microbicides triclosan and triclocarban on these outcomes and incidence of infection.Healthy pregnant women were identified and enrolled primarily at public clinics; their babies, enrolled shortly after birth, are followed to age 36?months. Automated weekly surveys assess daily health status, infectious disease symptoms, healthcare provider visits and antibiotic use, in the mother during pregnancy and the baby once born. At 4-monthly household visits, information and samples are collected from the mother (urine, stool, saliva, skin swab), the baby (blood by heel/toe stick, urine, stool, saliva, skin swab) and the household (environmental swabs). Annual blood samples are obtained by venipuncture (mother and baby). Medical charts are abstracted for allergy and infectious illness in the mother during pregnancy and the baby.From 7/2011 to 2/2015, 158 mothers were enrolled at approximately 20?weeks gestation; 127 babies were enrolled. Two-thirds of mothers are Hispanic, one-third are non-US born and one-third speak primarily Spanish; mean years of education is 13 (SD 6.2) years. Households have on average 4.5 residents. Most households (97%) were randomised to participate in the intervention. Completion of weekly surveys (86%) and follow-up (75% after 14?months) is excellent in this young, mobile population; collection of samples is ongoing with thousands of specimens stored.Enrolled babies will be followed until age 36?months (last anticipated visit: 07/2018) with medical chart review completed soon thereafter. All epidemiological information and samples will be available for collaborative hypothesis testing.NCT01442701; Pre-results.

Abstract

Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Picornaviridae family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate in vitro, hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike SAFV-3, HTCV-UC6 exhibited slow replication kinetics and demonstrated only a moderate cytopathic effect. Serologic assays revealed that 91% of U.S. adults carry antibodies to the genotype 2 cardioviruses, of which 80% generate neutralizing antibodies, in agreement with previous data showing that cardiovirus infection is widespread in humans. We also demonstrate an acute cardiovirus seroconversion event in a child with diarrhea and vomiting, thus reporting for the first time evidence linking cardiovirus infection to diarrheal disease in humans.

Abstract

Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis.We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04).H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

Abstract

Helicobacter pylori vaccines are under development to prevent infection. We quantified the cost-effectiveness of such a vaccine in the United States, using a dynamic transmission model.We compartmentalized the population by age, infection status, and clinical disease state and measured effectiveness in quality-adjusted life years (QALYs). We simulated no intervention, vaccination of infants, and vaccination of school-age children. Variables included costs of vaccine, vaccine administration, and gastric cancer treatment (in 2007 US dollars), vaccine efficacy, quality adjustment due to gastric cancer, and discount rate. We evaluated possible outcomes for periods of 10-75 years.H. pylori vaccination of infants would cost $2.9 billion over 10 years; savings from cancer prevention would be realized decades later. Over a long time horizon (75 years), incremental costs of H. pylori vaccination would be $1.8 billion, and incremental QALYs would be 0.5 million, yielding a cost-effectiveness ratio of $3871/QALY. With school-age vaccination, the cost-effectiveness ratio would be $22,137/QALY. With time limited to <40 years, the cost-effectiveness ratio exceeded $50,000/QALY.When evaluated with a time horizon beyond 40 years, the use of a prophylactic H. pylori vaccine was cost-effective in the United States, especially with infant vaccination.

Abstract

Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens [637 (89%) from patients with acute respiratory illness] and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic meningitis, encephalitis, and multiple sclerosis) revealed no evidence of cardiovirus infection. However, screening of 751 stool specimens from 498 individuals in a gastroenteritis cohort resulted in the detection of 6 additional cardioviruses (1.2%). Although all 8 human cardioviruses (including Saffold virus) clustered together by phylogenetic analysis, significant sequence diversity was observed in the VP1 gene (66.9%-100% pairwise amino acid identities). These findings suggest that there exists a diverse group of novel human Theiler's murine encephalomyelitis virus-like cardioviruses that hitherto have gone largely undetected, are found primarily in the gastrointestinal tract, can be shed asymptomatically, and have potential links to enteric and extraintestinal disease.

Abstract

Helicobacter pylori commonly infects humans; however, its mode of transmission remains unknown.To determine how humans-the primary host for H pylori-shed the organism into the environment.Controlled clinical experimental study conducted from February through December 1998.Clinical research unit of a hospital in northern California.Sixteen asymptomatic H pylori-infected and 10 uninfected adults.A cathartic (sodium phosphate) and an emetic (ipecac) were given to all infected subjects and an emetic was given to 1 uninfected subject.Confirmed H pylori isolates cultured from stool, air, or saliva before and after catharsis and emesis and from vomitus during emesis. Isolates were fingerprinted using repetitive extragenic palindromic (REP) polymerase chain reaction and species identity was confirmed by sequencing the 16s ribosomal RNA gene.All vomitus samples from infected subjects grew H pylori, often in high quantities. Air sampled during vomiting grew H pylori from 6 (37.5%) of the 16 subjects. Saliva before and after emesis grew low quantities of H pylori in 3 (18.8%) and 9 (56.3%) subjects, respectively. No normal stools and only 22 (21.8%) of 101 induced stools grew the organism, although 7 (50.0%) of 14 subjects had at least 1 positive culture (2 stool culture samples were contaminated by fungus and were not included). Fingerprints of isolates within subjects were identical to one another but differed among subjects. No samples from uninfected subjects yielded H pylori.Helicobacter pylori can be cultivated uniformly from vomitus and, occasionally, from saliva and cathartic stools. The organism is potentially transmissible during episodes of gastrointestinal tract illness, particularly with vomiting.

Abstract

Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma.This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay.Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0).Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.

Abstract

Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma.From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results.The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk.Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition.

Abstract

Probiotic use has skyrocketed in recent years. Little is known, however, about patient knowledge and practices regarding probiotic use, especially in the context of antibiotic use. An invitation to complete a short, anonymous, electronic survey was sent by email to 965 patients at a tertiary medical centre in California who had agreed to be contacted for participation in research studies. Questions were asked about both probiotic and antibiotic use in the prior three months. Of 333 survey respondents, 55% had recently used probiotics, including food products and/or supplements (90 and 60% of probiotic users, respectively). Women were more likely than men to have used probiotics (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.2-3.4). Health care providers (HCP) had prescribed antibiotics to 79 (24%) respondents in the preceding three months. Among antibiotic users, 33% had initiated or changed probiotics at the time of antibiotic use, usually without a recommendation from their prescribing HCP (72%). Only 12% of those who took probiotics with antibiotics had received a specific recommendation from their HCP. Most patients chose to take probiotic mixtures (56%), with few selecting evidence-based strains, such as Lactobacillus rhamnosus GG (11%). Regular probiotic use among patients is common. Typically, these probiotics are not recommended by a HCP, even in conjunction with antibiotic prescriptions. While a growing body of evidence supports specific probiotic strains for the prevention of antibiotic-associated diarrhoea, patients are often not receiving a specific recommendation from their HCP and appear to be taking strains without guidance from supporting evidence.

Abstract

Probiotics have rarely been studied in young healthy infants from low-income countries. This phase I study investigated the safety and acceptability of two probiotics in Bangladesh.Healthy infants aged four to twelve weeks from urban slums in Bangladesh were randomized to one of three different intervention dosing arms (daily, weekly, biweekly - once every two weeks) of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 over one month or to a fourth arm that received no probiotics. All subjects were followed for two additional months. Reported gastrointestinal and respiratory symptoms as well as breastfeeding rates, hospitalizations, differential withdrawals, and caretakers' perception of probiotic use were compared among arms.In total, 160 infants were randomized (40 to each arm) with 137 (Daily n?=?35, Weekly n?=?35, Biweekly n?=?35, Control n?=?32) followed up for a median of twelve weeks; 113 completed the study. Illness and breastfeeding rates were similar across all arms. Ten hospitalizations unrelated to probiotic use occurred. Forty eight percent of the caretakers of infants in intervention arms believed that probiotics improved their baby's health.These two commonly used probiotics appeared safe and well-accepted by Bangladeshi families.ClinicalTrials.gov NCT01899378 . Registered July 10, 2013.

Abstract

Interferon-gamma release assays have limited sensitivity for detecting latent tuberculosis infection. In this study, we determine if the addition of immunomodulators to the QuantiFERON-TB Gold In-Tube (QFT-GIT) increased test sensitivity without compromising specificity. We prospectively compared QFT-GIT results with and without incubation with 2 immunomodulators (lipopolysaccharide [LPS] and polyinosine-polycytidylic acid [PolyIC]) in 2 cohorts-113 culture-confirmed tuberculosis (TB) subjects in Hanoi, Vietnam, and 226 documented QFT-GIT-negative, low TB risk health care workers undergoing annual TB screening at a US academic institution. Sensitivity of the tests in TB subjects was 84.1% with the standard QFT-GIT and 85.8% and 74.3% after incubation with LPS and PolyIC, respectively. Specificity in low TB risk health care workers was 100% with the standard QFT-GIT by design and 86.7% with LPS and 63.3% with PolyIC. In conclusion, use of the 2 immunomodulators did not improve sensitivity of the QFT-GIT in TB patients and reduced specificity in low-risk health care workers.

Abstract

Daily dietary intake data derived from self-reported dietary recall surveys are widely considered inaccurate. In this study, methods were developed for adjusting these dietary recalls to more plausible values. In a simulation model of two National Health and Nutrition Examination Surveys (NHANES), NHANES I and NHANES 2007-2008, a predicted one-third of raw data fell outside a range of physiologically plausible bounds for dietary intake (designated a 33% failure rate baseline). To explore the nature and magnitude of this bias, primary data obtained from an observational study were used to derive models that predicted more plausible dietary intake. Two models were then applied for correcting dietary recall bias in the NHANES datasets: (a) a linear regression to model percent under-reporting as a function of subject characteristics and (b) a shift of dietary intake reports to align with experimental data on energy expenditure. After adjustment, the failure rates improved to <2% with the regression model and 4-9% with the intake shift model - both substantial improvements over the raw data. Both methods gave more reliable estimates of plausible dietary intake based on dietary recall and have the potential for more far-reaching application in correction of self-reported exposures.

Abstract

North American occupational health programs that switched from the tuberculin skin test (TST) to IFN-? release assays for latent tuberculosis screening are reporting challenges with interpretation of serial testing results in healthcare workers (HCWs). However, limited data exist on the reproducibility of serial IFN-? release assay results in low-risk HCWs.To evaluate the short-term reproducibility of QuantiFERON-TB Gold In-Tube (QFT) in a large cohort of HCWs and to define a QFT cutoff yielding a conversion rate equivalent to historical TST rates.We retrospectively evaluated the QFT results from HCWs with two or more QFT tests performed between June 2008 and July 2010 at an academic institution. Outcome measures were proportions of reproducibility, quantitative results, and conversion rates with alternate QFT cutoffs.A total of 9,153 HCWs with two or more QFT tests were included in the analysis. Of 8,227 individuals with a negative result, 4.4% (n = 361) converted their QFT result over 2 years. A total of 261 (72.3%) of the HCWs with conversions underwent repeat short-term testing after the first positive result with 64.8% reverting (n = 169). An IFN-? cutoff of 5.3 IU/ml or higher (manufacturer's cutoff is ?0.35 IU/ml) yielded a conversion rate of 0.4%, equal to our institution's historical TST conversion rate.The manufacturer's definition of QFT conversion results in an inflated conversion rate that is incompatible with our low-risk setting. A significantly higher QFT cutoff value is needed to match the historical TST conversion rate. Nonreproducible conversions in most converters suggested false-positive results.

Abstract

We screened 176 healthy, adult (aged 18-55 years) US refugees from tuberculosis (TB)-endemic countries to evaluate whether cytokine responses to latent TB infection (LTBI) are modified in the setting of concurrent H. pylori and helminth infection. As measured by the Quantiferon-TB GOLD interferon-? release assay, a total 38 (22%) subjects had LTBI, of which 28 (74%) also were H. pylori seropositive and/or helminth infected. Relative to ten subjects with LTBI only, 16 subjects with concurrent H. pylori infection had significantly elevated levels of IFN-?, and nine subjects with both H. pylori and helminth infection had significantly elevated levels of IFN-?, IL-2, IL-13, and IL-5. H. pylori is associated with enhanced IFN-? responses to TB, even in the setting of concurrent helminth infection. Efficacy of TB vaccines may vary with the co-existence of these three infections in the developing world.

Abstract

Beginning in 2005, the Centers for Disease Control and Prevention (CDC) expanded the overseas presumptive treatment of intestinal parasites with albendazole to include refugees from the Middle East. We surveyed the prevalence of helminths and protozoa in recent Middle Eastern refugees (2008-2010) in comparison with refugees from other geographical regions and from a previous survey (2001-2004) in Santa Clara County, California. Based on stool microscopy, helminth infections decreased, particularly in Middle Eastern refugees (0.1% versus 2.3% 2001-2004, P = 0.01). Among all refugees, Giardia intestinalis was the most common protozoan found. Protozoa infections also decreased somewhat in Middle Eastern refugees (7.2%, 2008-2010 versus 12.9%, 2001-2004, P = 0.08). Serology for Strongyloides stercoralis and Schistosoma spp. identified more infected individuals than stool exams. Helminth infections are increasingly rare in refugees to Northern California. Routine screening stool microscopy may be unnecessary in all refugees.

Abstract

Triclosan-a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies-has the potential to alter both gut microbiota and endocrine function and thereby affect body weight.We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003-2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures-either presence vs. absence or quartiles of triclosan-we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations.Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p?=?0.002), and 0.3 (p?=?0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (??=?0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified.Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.

Abstract

We investigated a sudden increase in the rate of positive QuantiFERON-TB Gold In-Tube results from 10% to 31% at a U.S. academic institution. Direct comparison of the TB antigen tubes with tubes from a different lot number identified that a potential problem with the TB antigen vials in a certain tube lot was the likely cause of the elevated positive rate. The underlying defect remains unknown. This finding warrants refinement of quality control programs by the manufacturer and users.

Abstract

In a cohort of 1,863 Filipinos, diarrhea, fever, and unsanitary conditions in infancy were associated with a decreased body mass index in adulthood; upper respiratory tract infection was associated with an increased body mass index. These finding support the hypothesis that infections early in life play a role in body habitus in adulthood.

Abstract

Better understanding about gastric cancer incidence patterns among Hispanics by birthplace, socioeconomic status (SES), and acculturation can improve preventive strategies and disease models.Incidence rates, rate ratios, and estimated annual percent change (EAPC) in rates of anatomic and histologic subtype-specific gastric cancer were calculated by age, sex, and nativity among Hispanics using California Cancer Registry data from 1988 through 2004. Incidence rates in 1998 to 2002 were compared by neighborhood SES and Hispanic enclave status according to 2000 US Census data.Incidence rates of diffuse gastric cancer increased from 1988 through 2004 among foreign-born Hispanic men (EAPC: 3.5%, 95% CI: 1.5%-5.5%) and U.S.-born Hispanic women (EAPC: 3.0%, 95% CI: 0.7%-5.3%). During the same time period, incidence rates of intestinal gastric cancer declined significantly and both cardia and noncardia gastric cancer were steady or declined among foreign-born and U.S.-born Hispanic men and women. Noncardia and both intestinal and diffuse gastric cancer were more common in foreign-born than U.S.-born Hispanic men and women, and in those from lower SES, higher enclave neighborhoods. By contrast, among younger and middle-aged Hispanic men, cardia tumors were more common in the U.S.-born than the foreign-born, and in higher SES, lower enclave neighborhoods.Varying gastric cancer risk factors among Hispanic subgroups and increasing rates of diffuse gastric cancer in foreign-born Hispanic men and U.S.-born Hispanic women merit further investigation to identify separate disease etiologies.Age, sex, birthplace, SES, and acculturation modify gastric cancer incidence in Hispanics and should be considered when examining disease risk and prevention.

Abstract

Polyomaviruses are small circular DNA viruses associated with chronic infections and tumors in both human and animal hosts. Using an unbiased deep sequencing approach, we identified a novel, highly divergent polyomavirus, provisionally named MX polyomavirus (MXPyV), in stool samples from children. The ?5.0 kB viral genome exhibits little overall homology (<46% amino acid identity) to known polyomaviruses, and, due to phylogenetic variation among its individual proteins, cannot be placed in any existing taxonomic group. PCR-based screening detected MXPyV in 28 of 834 (3.4%) fecal samples collected from California, Mexico, and Chile, and 1 of 136 (0.74%) of respiratory samples from Mexico, but not in blood or urine samples from immunocompromised patients. By quantitative PCR, the measured titers of MXPyV in human stool at 10% (weight/volume) were as high as 15,075 copies. No association was found between the presence of MXPyV and diarrhea, although girls were more likely to shed MXPyV in the stool than boys (p=0.012). In one child, viral shedding was observed in two stools obtained 91 days apart, raising the possibility of chronic infection by MXPyV. A multiple sequence alignment revealed that MXPyV is a closely related variant of the recently reported MWPyV and HPyV10 polyomaviruses. Further studies will be important to determine the association, if any, of MXPyV with disease in humans.

Abstract

Average tuberculosis (TB) incidence rates are high in Canadian Aboriginal communities, but there is significant variability within this group.To determine whether local history of post-contact TB epidemics is predictive of contemporary epidemiology among Aboriginal communities in Saskatchewan, Canada.TB incidence, age-specific morbidity patterns and rates of clustering of TB genotypes from 1986 to 2004 were compared between two groups of communities: Group 1, in which post-contact epidemics of TB were established around 1870, and Group 2, in which they were delayed until after 1920. Concomitant effects of socio-economic and geographic variables were explored with multivariate models.Group 2 communities were characterized by higher annual incidence of TB (median 431 per 100,000 population vs. 38/100,000). In multivariate models that included socio-economic and geographic variables, historical grouping remained a significant independent predictor of community incidence of TB. Clustering of TB genotypes was associated with Group 2 (OR 8.7, 95%CI 3.3-22.7) and age 10-34 years (OR 2.5, 95%CI 1.1-5.7).TB transmission dynamics can vary significantly as a function of a population's historical experience with TB. Populations at different stages along the epidemic trajectory may be amenable to different types of interventions.

Abstract

More than one-third of the world's population, or over 2 billion people, are infected with Mycobacterium tuberculosis, the causative pathogen of tuberculosis in humans. Why only 10% of those infected develop active disease while the remainder harbor latent infection remains one of the greatest scientific and public health mysteries. Bacterial persistence is characterized by a dynamic state of immunological tolerance between pathogen and host. The critical role of CD4(+) T cells in defense against intracellular pathogens became evident during epidemiological studies of HIV-1 infection, which showed a clear inverse relationship between CD4(+) T-cell count in peripheral blood and increased risk of infection with M. tuberculosis, pneumocystis and Toxoplasma gondii. There is also growing evidence of a common mucosal immune system, whereby immune cells activated at one mucosal site may disseminate to remote effector sites. In this commentary, we review emerging evidence from human studies that the outcome of M. tuberculosis infection is influenced by concurrent mucosal infections, using Helicobacter pylori and geohelminths as examples. Understanding how the complexity of microbial exposures influences host immunity may have important implications for vaccine development and therapeutic interventions.

Abstract

Interferon-release assays (IGRAs) represent advances in tuberculosis immunology and evolutionary biology. IGRAs were designed to replace tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection because of their logistical advantages and enhanced specificity over TST. Although IGRAs and TST have been useful in epidemiologic studies, they lack the sensitivity and reproducibility normally expected from diagnostic tests in clinical practice. In this review, we present an overview of the current recommendations and knowledge in the field and discuss practical approaches in areas of uncertainty related to discordant IGRA results.

Abstract

Although scientific knowledge in viral oncology has exploded in the 20th century, the role of bacteria as mediators of oncogenesis has been less well elucidated. Understanding bacterial carcinogenesis has become increasingly important as a possible means of cancer prevention. This review summarizes clinical, epidemiological, and experimental evidence as well as possible mechanisms of bacterial induction of or protection from malignancy.

Abstract

In vitro gamma interferon release assays (IGRAs) are increasingly used as an alternative to the traditional tuberculin skin test for the diagnosis of latent Mycobacterium tuberculosis infection. Evaluation of the QuantiFERON-TB Gold in-tube assay (QFT-IT) prior to large-scale implementation at the Stanford Hospital and Clinics for a health care worker screening program revealed a critical preanalytical factor affecting the results. We found that incubation delay significantly increased the frequency of indeterminate results. In this study, QFT-IT was performed with samples from healthy volunteers, and replicate tubes were incubated at 37 degrees C either immediately or after a delay at room temperature for 6 and 12 h. No indeterminate results (0/41) were seen when the assay was performed with immediate incubation. Incubation delays of 6 and 12 h yielded indeterminate results at rates of 10% (2/20) (P = 0.10) and 17.1% (7/41) (P = 0.01), respectively. The increased rate of indeterminate results was due to a decrease in the mean values for the mitogen-nil tubes when incubation was delayed for 6 h (P = 0.004) and 12 h (P < 0.001). The rates of concordance of positive or negative results obtained following immediate incubation and following 6- and 12-h delays were 77.8% (14/18) and 79.4% (27/34), respectively. Subsequent implementation of the immediate incubation procedure in our screening program for 14,830 health care workers yielded an indeterminate result rate of 0.36% over a period of 12 months, a significant improvement over the reported rates of 5 to 40% for QFT-IT. We conclude that immediate incubation of QFT-IT tubes is an effective way to minimize indeterminate results. The effect of incubation delay on the accuracy of QFT-IT remains to be determined.

Abstract

To assess the association between vitamin D deficiency and tuberculosis disease progression, we studied vitamin D levels in a cohort of tuberculosis patients and their contacts (N = 129) in Pakistan. Most (79%) persons showed deficiency. Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis.

Abstract

Many medical curricula now include programs that provide students with opportunities for scholarship beyond that provided by their traditional, core curricula. These scholarly concentration (SC) programs vary greatly in focus and structure, but they share the goal of producing physicians with improved analytic, creative, and critical-thinking skills. In this article, the authors explore models of both required and elective SC programs. They gathered information through a review of medical school Web sites and direct contact with representatives of individual programs. Additionally, they discuss in-depth the SC programs of the Warren Alpert Medical School of Brown University; the University of South Florida College of Medicine; the University of California, San Francisco; and Stanford University School of Medicine. The authors describe each program's focus, participation, duration, centralization, capstone requirement, faculty involvement, and areas of concentration. Established to address a variety of challenges in the U.S. medical education system, these four programs provide an array of possible models for schools that are considering the establishment of an SC program. Although data on the impact of SC programs are lacking, the authors believe that this type of program has the potential to significantly impact the education of medical students through scholarly, in-depth inquiry and longitudinal faculty mentorship.

Abstract

For more than 40 years, the faculties of Duke University School of Medicine (SOM) and Stanford University SOM have encouraged or required students to engage in scholarship as a way to broaden their education and attract them to careers in academic medicine. A dedicated period of research was first integrated into the Duke curriculum in 1959 to provide an opportunity for students to develop into physician leaders through a rigorous scholarly experience in biomedically related research. Originally designed to foster experience in laboratory-based basic research, the third-year program has evolved in response to the changing landscape of medicine and shifting needs and career interests of the medical student population. Stanford University SOM also has a long-standing commitment to biomedical research and currently requires each student to complete an in-depth, mentored "scholarly concentration." In contrast to Duke, where most of the scholarly research experiences take place in an immersive third year, the Stanford program encourages a longitudinal, multiyear exposure over all four (or five) years of medical school. Although the enduring effects of embedding a rigorous research program are not yet fully known, preliminary data suggest that these experiences instill an appreciation for research, impart research rigor and methodologies, and may motivate students to pursue careers in academic medicine. The authors discuss the histories, evolution, logistics, and ongoing challenges of the research programs at Duke University SOM and Stanford University SOM.

Abstract

The ability to understand and integrate new knowledge into clinical practice is a necessary quality of good physicians. Student participation in in-depth scholarship could enhance this skill in physicians while also creating a larger cadre of physician-scientists prepared to advance the field of medicine. However, because no definitive data exist demonstrating that in-depth scholarship in medical school leads to improved patient care or to productive academic careers, whether such scholarship should be required as part of the medical school curriculum is unclear. In this article, the authors present both sides of this debate. Theoretical benefits to students of a required scholarly program include closer mentorship by individual faculty, enhanced capabilities in critical interpretation of research findings, and increased confidence to investigate conundrums encountered in clinical care. Society may also benefit by having physicians available to create and apply new knowledge related to biomedicine. These theoretical benefits must be balanced, however, by pragmatic considerations of required scholarly projects including their impact on medical school applications, their effect on the medical curriculum, their costs, the availability of mentors, and their effects on the school's educational culture.

Abstract

Gastric cancer is the second most common cause of cancer death worldwide. A large body of evidence supports a causal role of Helicobacter pylori in the majority of gastric malignancies. Great strides have been made in understanding the pathogenesis of this relationship, but much remains to be learned. Moreover, because of the high prevalence of infection, the lack of definitive trials, and the challenges of H. pylori treatment, there remains no consensus on the role of routine screening and treatment of this infection to prevent cancer. This article reviews the current knowledge on H. pylori and gastric cancer and presents some of the clinical and public health challenges associated with this pathogen.

Abstract

Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not found in approximately 30-50% of cases. Picornaviral genera such as enterovirus, kobuvirus, cosavirus, parechovirus, hepatovirus, teschovirus, and cardiovirus have all been found in human and animal diarrhea. Modern technologies, especially deep sequencing, allow rapid, high-throughput screening of clinical samples such as stool for new infectious agents associated with human disease.A pool of 141 pediatric gastroenteritis samples that were previously found to be negative for known diarrheal viruses was subjected to pyrosequencing. From a total of 937,935 sequence reads, a collection of 849 reads distantly related to Aichi virus were assembled and found to comprise 75% of a novel picornavirus genome. The complete genome was subsequently cloned and found to share 52.3% nucleotide pairwise identity and 38.9% amino acid identity to Aichi virus. The low level of sequence identity suggests a novel picornavirus genus which we have designated klassevirus. Blinded screening of 751 stool specimens from both symptomatic and asymptomatic individuals revealed a second positive case of klassevirus infection, which was subsequently found to be from the index case's 11-month old twin.We report the discovery of human klassevirus 1, a member of a novel picornavirus genus, in stool from two infants from Northern California. Further characterization and epidemiological studies will be required to establish whether klasseviruses are significant causes of human infection.

Abstract

Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer.

Abstract

Gastric colonization with Helicobacter pylori is a proposed protective factor against gastroesophageal reflux disease (GERD), but little population-based data exist and other data conflict.We conducted a case-control study within the membership of a large integrated health-care system that compared GERD-free subjects with two groups: subjects with a physician-assigned GERD diagnosis and randomly selected members with self-described weekly GERD symptoms. Subjects completed interviews, GERD questionnaires, and antibody testing for H. pylori and its cagA protein.Serologic data were available for 301 physician-assigned GERD patients, 81 general membership subjects with GERD symptoms, and 175 general membership subjects without GERD symptoms. Physician-assigned GERD patients were less likely to have H. pylori antibodies than GERD-free member controls (odds ratio (OR) = 0.27, 95% confidence interval (CI) 0.15-0.47); there was also an inverse association between H. pylori and GERD symptom severity (OR = 0.18, 95% CI 0.08-0.41; severe or very severe symptoms) and GERD frequency (OR = 0.18, 95% CI 0.09-0.38; for symptoms at least weekly). The association was stronger among persons with erosive GERD and was similar between H. pylori-positive subjects with and without cagA. There was no association among persons who were cagA positive, but H. pylori negative. Similar findings were found in analyses of the general membership with self-described GERD symptoms.H. pylori antibody status was inversely associated with a GERD diagnosis and GERD symptoms compared with a general membership population.

Abstract

We describe a method of working on publicly available data to estimate disease prevalence in small geographic areas using Helicobacter pylori as a model infection. Using data from the Third National Health and Nutrition Examination Survey, risk parameters for H. pylori infection were obtained by logistic regression and validated by predicting 737.5 infections in an independent cohort with 736 observed infections. The prevalence of H. pylori infection in the San Francisco Bay Area was estimated with the probabilities obtained from a predictive logistic model, using risk parameters with individual-level 1990 U.S. Census data as input. Predicted H. pylori prevalence was also compared to gastric cancer incidence obtained from the Northern California Cancer Center and showed a positive correlation with gastric cancer incidence (P<0.001, R2=0.87), and no statistically significant association with other malignancies. By exclusively using publicly available data, these methods may be applied to selected conditions with strong demographic predictors.

Abstract

Gastric colonisation with the Helicobacter pylori bacterium is a proposed protective factor against oesophageal adenocarcinoma, but its point of action is unknown. Its associations with Barrett's oesophagus, a metaplastic change that is a probable early event in the carcinogenesis of oesophageal adenocarcinoma, were evaluatedA case-control study was carried out in the Kaiser Permanente Northern California population, a large health services delivery organisation. Persons with a new Barrett's oesophagus diagnosis (cases) were matched to subjects with gastro-oesophageal reflux disease (GORD) without Barrett's oesophagus and to population controls. Subjects completed direct in-person interviews and antibody testing for H pylori and its CagA (cytotoxin-associated gene product A) protein.Serological data were available on 318 Barrett's oesophagus cases, 312 GORD patients and 299 population controls. Patients with Barrett's oesophagus were substantially less likely to have antibodies for H pylori (OR = 0.42, 95% CI 0.26 to 0.70) than population controls; this inverse association was stronger among those with lower body mass indexes (BMIs < 25, OR = 0.03, 95% CI 0.00 to 0.20) and those with CagA+ strains (OR = 0.08, 95% CI 0.02 to 0.35). The associations were diminished after adjustment for GORD symptoms. The H pylori status was not an independent risk factor for Barrett's oesophagus compared with the GORD controls.Helicobacter pylori infection and CagA+ status were inversely associated with a new diagnosis of Barrett's oesophagus. The findings are consistent with the hypothesis that H pylori colonisation protects against Barrett's oesophagus and that the association may be at least partially mediated through GORD.

Abstract

Infection with Helicobacter pylori is an established risk factor for gastric cancer. Results from two studies suggest that it may also be a risk factor for pancreatic cancer.We conducted a nested case control study among 128,992 adult subscribers to the Kaiser Permanente Medical Care Program who had been enrolled in a multiphasic health checkup from 1964 to 1969. Serum collected during the checkup was maintained frozen, and subjects were followed for cancer. Cases consisted of 104 randomly selected subjects among 507 who developed pancreatic cancer in the cohort. Controls consisted of 262 pancreatic cancer-free subjects from a pool of 730 controls previously tested for studies conducted on this cohort. Controls were individually matched to cases on age, gender, race, site, and date of multiphasic health checkup. Control sera were compared with cases for antibodies to H. pylori and the CagA protein. The effects of smoking, alcohol consumption, obesity, and years of education were also investigated.Neither H. pylori [odds ratio (OR), 0.85; 95% confidence interval (95% CI), 0.49-1.48] nor its CagA protein (OR, 0.96; 95% CI, 0.48-1.92) was associated with subsequent development of pancreatic cancer. Smoking (OR, 2.09; 95% CI, 1.17-3.74) and greater number of years of education (OR, 2.13; 95% CI, 1.23-3.69) were risk factors for pancreatic cancer, whereas alcohol consumption and obesity were not.Our results suggest that H. pylori infection is not associated with development of pancreatic cancer.

Abstract

Studies are needed to characterize the reproducibility of QuantiFERON-TB Gold (QFT-G) for targeted U.S. screening populations. Members of northern California households were tested with the QFT-G in-tube assay (QFT-G-IT) at two home visits 3 months apart. Reproducibility and agreement with the tuberculin skin test (TST) were assessed. Monte Carlo simulation was used to evaluate the role of test-related error. Of 63 individuals (49 adults and 14 children) completing QFT-G-IT at both time points, 79% were foreign-born (98% from Latin America) and 68% reported Mycobacterium bovis BCG vaccination. At the baseline visit, 23 (37%) were TST positive and 15 (24%) were QFT-G-IT positive (kappa = 0.48 [+/- 0.11]). At 3 months, 3/48 (6.3%; 95% confidence interval [95CI], 2 to 17) of those initially QFT-G-IT negative converted, and 5/15 (33%; 95CI, 15 to 58) of those initially QFT-G-IT positive reverted. Among the 8 individuals with inconsistent QFT-G-IT results, the maximum gamma interferon response at either visit was 0.68 IU/ml versus means of 4.99 (+/- 3.74) and 6.95 (+/- 5.6) for 10 persistent positives at the first and second visits, respectively. Expected false-reversion and -conversion rates were 32% (90CI, 25 to 39%) and 6.95% (90CI, 4.6 to 9.8%) when the sensitivity and specificity were assumed to average 70% and 98%, respectively. Transient responses to QFT-G-IT are common, and low positive results need to be interpreted with caution. Further studies are needed to characterize the predictive value of the test for U.S. foreign-born and other targeted screening populations.

Abstract

Primary human cerebral myiasis is an exceedingly rare condition and is almost never encountered by physicians in developed countries. The case report summarizes a case of extensive cerebral myiasis in a periurban community in the United States.After a minor motor vehicle accident, police brought a 75-year-old man to the emergency room because he was observed to have a large cranial lesion. Examination revealed a 15 x 17 cm frontal bone defect with eroded frontal dura, exposed cortex, and massive cortical maggot infestation.The patient was empirically treated with intravenous antibiotics for meningitis. Maggots (Phaenicia sericata, or the green bottle fly) were removed by suction, attrition, and gentle contact exposure to a mild bleach solution. Biopsy of the scalp and cranium revealed angiosarcoma, for which operative treatment was refused. The patient was transferred to a skilled nursing facility for palliative care where he died 3 months later.This is the first published case of cerebral myiasis in the United States. Although human cerebral myiasis is rare, conditions do exist in this country that permit myiasis.

Abstract

Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux.We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls).A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR=0.18 [CI 0.04-0.78]). This inverse association was seen only in overweight subjects (BMI>or=25, P value for interaction=0.09). The effects of H. pylori and ghrelin were independent.Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.

Abstract

Although most of Helicobacter pylori-related diseases are associated with male gender, the role of gender as a risk factor for H. pylori infection is still debated. To assess the true association between H. pylori and gender, we conducted a meta-analysis of large, population-based studies where the measure of association had been adjusted at least for age and socioeconomic status, and obtained primary data from authors when information on gender associations were not presented. In 18 adult populations, the test of heterogeneity was not significant and male gender was significantly associated with H. pylori infection (summary odds ratio [OR] 1.16 [95% confidence interval (CI) 1.11, 1.22]). In 10 pediatric populations, the test of heterogeneity was of borderline significance, and the summary OR computed using a random effect model was close to 1 (summary OR 1.03 [95% CI 0.91, 1.17]). This study confirms the male predominance of H. pylori infection in adults as a global and homogeneous phenomenon; such predominance is not apparent in children. Differential antibiotic exposure or differential protective immunity between genders may explain the different results observed between children and adult studies.

Abstract

The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4-17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection.

Abstract

Socially housed rhesus monkeys rapidly acquired Helicobacter pylori infection, although the organism was rarely cultivated from saliva, feces, or the environment. Since the concentrations of H. pylori in vomit were compatible with what is known about the infectious dose, our results are most consistent with an oral-oral means of transmission.

Abstract

Helicobacter pylori is transmitted within households and high concordance is observed among siblings. To better understand the contributions of close interpersonal contact and family relatedness to transmission, we compared concordance of H. pylori infection among 241 sibling and non-sibling children aged 2-18 years in 68, predominantly low-income, Hispanic households with at least two nuclear families. Prevalence of H. pylori infection was 24%. Compared to children with no infected siblings or non-siblings and adjusting for age, odds of H. pylori infection were 1.2 (95% CI 0.52-2.9), 3.2 (95% CI 1.14-9.1), and 9.4 (95% CI 3.1-28.5) for children residing with at least one infected non-sibling, one infected sibling, and with at least one infected sibling and non-sibling, respectively. The study further implicates intersibling transmission as a pathway for H. pylori infection in childhood. In addition, living with a non-sibling in extended-family homes may contribute to infection risk but only in households with prevalent H. pylori infection within all family groups.

Abstract

Six cases of coagulase-negative staphylococcal mediastinitis were identified in the latter half of 1999. A new preoperative cleansing solution was suspected by hospital staff to be a factor in the outbreak. We evaluated this possible risk factor along with other known and suspected surgical site infection risk factors in this case-control study.

Abstract

Inflammatory markers predict cardiovascular risk and mortality in endstage renal disease. The relationship of chronic infections to inflammation and vascular disease events has not been reported among American dialysis patients.We performed a cross-sectional and prospective study of a multiracial cohort of 97 chronic hemodialysis patients in California. Anti-Chlamydia pneumoniae IgA and IgG antibodies (Cp-IgA and Cp-IgG), anti-Helicobacter pylori antibodies (Hp-IgG), and highly sensitive C-reactive protein (hsCRP) levels were measured at enrollment. We ascertained the prevalence of atherosclerotic vascular (coronary artery, cerebrovascular, and peripheral vascular) disease (AVD) events, and observed participants for at least 1 year for incident events and mortality. We defined statistical significance as P < 0.01.Elevated hsCRP levels (77%) and seropositivity to C. pneumoniae were common (Cp-IgA, 49%; Cp-IgG, 64%), whereas the seroprevalence of Hp-IgG was relatively low (25%). The hsCRP levels did not vary with infection status. In bivariate analysis, Cp-IgA and Cp-IgG were each associated with approximately fourfold higher odds of prevalent AVD (P < 0.01). Although anti-chlamydial antibodies maintained nearly significant associations with AVD after covariate adjustment (P < 0.05), antibodies did not predict outcomes over the period of observation. However, hsCRP was a nearly significant independent predictor of prevalent AVD (P = 0.02) and of mortality during follow-up (P = 0.01). We did not detect an association of Hp-IgG with any study outcome.Our findings generalize a possible link between C. pneumoniae and prevalent atherosclerosis in American hemodialysis patients and confirm the importance of hsCRP as a prognostic indicator. Our work does not support H. pylori as an important mediator of cardiovascular risk in dialysis patients.

Abstract

Helicobacter pylori causes gastric preneoplasia and neoplasia. Eradicating H. pylori can result in partial regression of preneoplastic lesions; however, the molecular underpinning of this change is unknown. To identify molecular changes in the gastric mucosa following H. pylori eradication, we used cDNA microarrays (with each array containing approximately 30,300 genes) to analyze 54 gastric biopsies from a randomized, placebo-controlled trial of H. pylori therapy. The 54 biopsies were obtained from 27 subjects (13 from the treatment and 14 from the placebo group) with chronic gastritis, atrophy, and/or intestinal metaplasia. Each subject contributed one biopsy before and another biopsy 1 year after the intervention. Significant analysis of microarrays (SAM) was used to compare the gene expression profiles of pre-intervention and post-intervention biopsies. In the treatment group, SAM identified 30 genes whose expression changed significantly from baseline to 1 year after treatment (0 up-regulated and 30 down-regulated). In the placebo group, the expression of 55 genes differed significantly over the 1-year period (32 up-regulated and 23 down-regulated). Five genes involved in cell-cell adhesion and lining (TACSTD1 and MUC13), cell cycle differentiation (S100A10), and lipid metabolism and transport (FABP1 and MTP) were down-regulated over time in the treatment group but up-regulated in the placebo group. Immunohistochemistry for one of these differentially expressed genes (FABP1) confirmed the changes in gene expression observed by microarray. In conclusion, H. pylori eradication may stop or reverse ongoing molecular processes in the stomach. Further studies are needed to evaluate the use of these genes as markers for gastric cancer risk.

Abstract

Although gastric hypochlorhydria is a risk factor for gastroenteritis and for gastric cancer, no reliable, inexpensive, noninvasive test exists for screening or epidemiologic studies. We aimed to evaluate the sensitivity and specificity of the blood quininium resin test (bQRT) for hypochlorhydria, against pH monitoring. Twelve fasting adult volunteers-seven with and five without H. pylori infection-ingested 80 mg/kg of quininium resin twice, once with and once without acid suppression. Gastric pH was monitored for 75 minutes; serum samples were obtained at times 0 and 75 minutes. The bQRT levels were compared to gastric pH, controlling for omeprazole use and H. pylori infection. Subjects with a median recorded pH > or =3.5 were considered hypochlorhydric. Using a bQRT level of 10 as a cutoff for hypochlorhydria, the sensitivity and specificity of the bQRT were 100% and 37.5%, respectively. The bQRT predicted omeprazole use more accurately than pH monitoring. In conclusions, The bQRT has a high sensitivity for hypochlorhydria, making it potentially useful in populations with a high prevalence of hypochlorhydria. In its current formulation, the bQRT's low specificity makes it less useful in low-risk population.

Abstract

Results of clinical trials that have assessed whether gastric cancer is preventable with Helicobacter pylori eradication therapy remain inconclusive. These trials have used atrophy, intestinal metaplasia, and dysplasia as histopathologic end points that reflect possible preneoplastic lesions. Trial results would be more compelling if cell proliferation and inflammatory markers improved simultaneously with histopathologic lesions.To study the presence of cell proliferation markers and type of inflammatory cells in biopsy specimens with gastritis, atrophy, and intestinal metaplasia before and 1 year after H pylori therapy and to determine if immunohistochemistry can be used to study these.We evaluated 12 subjects with gastritis and 16 with gastritis and multiple foci of atrophy and intestinal metaplasia by using immunohistochemical assays for tumor suppressor protein p53, proliferation marker Ki-67, cell cycle regulator cyclin D1, T and B lymphocytes, macrophages, and TUNEL (terminal deoxynucleotide transferase deoxyuridine triphosphate nick end labeling) assay for apoptosis. The biopsy specimens were selected from a randomized clinical trial that studied improvement of histopathologic gastric lesions after H pylori eradication.Groups of surface epithelial cells that expressed p53 and Ki-67 were observed more often in subjects with atrophy and intestinal metaplasia compared with those with gastritis alone. T lymphocytes in the lamina propria were frequently observed 1 year after treatment in subjects with atrophy and intestinal metaplasia.Immunohistochemical assays for cell proliferation and inflammatory cell markers showed different distribution patterns in these gastric biopsy specimens. The presence of T lymphocytes and groups of cells that expressed proliferation markers in subjects with multiple foci of atrophy and intestinal metaplasia needs further study.

Abstract

Santa Clara County, Northern California.To characterize agreement of tuberculin skin test (TST) and QuantiFERON-TB (QFT) with repeated testing.Fifty-two subjects participating in an ongoing prospective study of infectious disease transmission were tested by TST and QFT at two home visits 3 months apart. Boosting was defined as reclassification of TST from negative to positive. Agreement and reproducibility of TST and QFT were assessed using kappa and McNemar statistics.Of 48 individuals completing all tests, 75% were foreign-born (92% Latin America) and 58% were BCG-vaccinated. Initial TST and QFT were positive in 13 (27%) and 21 (44%), respectively, with an overall agreement of 67% (K = 0.29). Ten (29%) of 35 initial TST-negative reactions boosted, nine of whom were BCG-vaccinated subjects. Boosting occurred in eight (67%) of 12 subjects who were initially QFT-positive/TST-negative. Compared to the second TST, initial QFT had a relative post-test probability of 76% (95% CI 0.58-0.95); boosting accounted for 8/16 (50%) of initial testing discordances.Positive QFT in the setting of negative TST frequently anticipates a TST boost. This finding helps explain discordance between the two tests and may provide an alternative to serial TST testing.

Abstract

To quantify the contributions of household and environmental factors to Helicobacter pylori infection, the authors examined H. pylori infection among several generations of Hispanics in the San Francisco Bay Area. Between 2000 and 2004, household members were tested for H. pylori and interviewed about demographic factors and household pedigree. An immigrant was defined as someone born in Latin America with at least one Latin America-born parent; a first-generation US-born Hispanic was defined as someone born in the United States with at least one Latin America-born parent; and a second-generation US-born Hispanic was defined as someone born in the United States with at least one US-born parent. Prevalences of H. pylori in immigrants and first- and second-generation US-born Hispanics were 31.4% (102/325), 9.1% (98/1,076), and 3.1% (2/64), respectively. Compared with second-generation US-born Hispanics, the age-adjusted odds ratios for H. pylori were 9.70 (95% confidence interval (CI): 1.57, 60.00) for immigrants and 4.32 (95% CI: 0.69, 26.96) for first-generation US-born Hispanics (p(trend) < 0.001). These odds ratios decreased to 6.19 (95% CI: 1.13, 33.77) and 3.24 (95% CI: 0.59, 17.82), respectively, after adjustment for parental infection (odds ratio (OR) = 2.94, 95% CI: 1.59, 4.38), low education (OR = 1.76, 95% CI: 1.20, 2.68), and crowding (OR = 1.23, 95% CI: 0.84, 1.79). Both the household and birth-country environments probably contributed to declining H. pylori prevalence among successive generations of Hispanics.

Abstract

With continuing emigration from endemic countries, screening for parasitic infections remains a priority in U.S. communities serving refugee and immigrant populations. We report the prevalence of helminths and protozoa as well as demographic risk factors associated with these infections among 533 refugees seen at the Santa Clara County, California, Refugee Clinic between October 2001 and January 2004. Stool parasites were identified from 14% of refugees, including 9% found to have one or more protozoa and 6% found to have at least one helminth. Most common protozoan infections were Giardia lamblia (6%) and Dientamoeba fragilis (3%), and for helminths, hookworm (2%). Protozoa were more frequent in refugees < 18 years of age (OR: 2.2 [1.2-4.2]), whereas helminths were more common in refugees from South Central Asia (OR: 8.0 [2.3-27.7]) and Africa (OR: 5.9 [1.6-21.6]) when compared with refugees from Eastern Europe and the Middle East. Among helminths, Ascaris lumbricoides and hookworm were concentrated among South Central Asians (6 of 7 and 10 of 11 cases, respectively), whereas Strongyloides stercoralis was predominantly found in Africans (5 of 7 cases). Although predeparture empirical treatment programs in Saharan Africa may have helped to reduce prevalence among arriving refugees from this region, parasitic infection is still common among refugees to the United States with helminth infections found in more specific populations. As refugees represent only a fraction of recent immigrants from endemic countries, current studies in nonrefugee groups are also needed.

Abstract

Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality, but use is limited. A barrier to ITN use may be lack of knowledge regarding malaria transmission and prevention. This study is a controlled trial comparing ITN use and malaria knowledge levels between households in Piron, Mali, undertaken in 2003.Households received net impregnation services either with or without antecedent education. The main outcome measure was ITN use, defined as impregnation of at least one of the household's existing bednets with insecticide during the study. Knowledge about malaria and prevention practices was assessed pre- and post- educational intervention. Results were analysed by household and by individual.Forty-nine percent (34/70) of households who received the educational component impregnated their nets in comparison to 35% (22/62) of households who did not (OR = 1.6 CI = 0.8-3.3, P = 0.19). In individual analysis, ITN use was significantly greater in participants who had received the educational intervention (48%) vs. individuals who did not (33%, OR = 1.9, P = 0.012). Knowledge levels about malaria significantly increased for each individual pre- versus post- educational intervention (average change score = 2.13, standard deviation = 1.97, t = -17.78, P < 0.001), although there was no difference found between educational (change score = 2.14) and control groups (change score = 2.12).It is possible to educate individuals about malaria and to implement net impregnation services with limited resources. Greater accessibility to net-impregnation services is necessary but not sufficient to increase ITN use.

Abstract

Transmission of infectious gastroenteritis was studied in 936 predominately Hispanic households in northern California. Among 3,916 contacts of 1,099 primary case-patients, the secondary attack rate was 8.8% (95% confidence interval 7.9-9.7); children had a 2- to 8-fold greater risk than adults. Bed-sharing among children in crowded homes is a potentially modifiable risk.

Abstract

In young children, the significance of stool samples transiently positive for Helicobacter pylori antigen is unknown. As part of a larger prospective study on enteric infections, stool samples were obtained from 323 children at two time points 3 months apart and tested for H. pylori antigen using a commercially available enzyme-linked immunosorbent assay (ELISA) test. Seminested PCR for a Helicobacter-specific 16S rRNA gene was performed on all 26 pairs reverting from positive to negative (transient positives), all 4 persistent antigen-positive pairs, and 10 randomly selected persistent antigen-negative pairs. Helicobacter species were amplified from the first stool samples of 15/26 (58%) of the transient positives and 1 (25%) of 4 persistent positives. No Helicobacter species were amplified from the 10 persistent negatives. Among the 15 amplicons from transient-positive stool, H. pylori was sequenced and identified from 12 (80%; 95% confidence interval, 52% to 96%) and other Helicobacter spp. were identified from three (Helicobacter canis, Helicobacter winghamensis, and MIT 99-5504). Four of the 15 remained positive by PCR for the second (antigen-negative) stool sample, including all 3 initially identified as non-H. pylori. Helicobacter bilis was amplified from the second sample of a persistent positive. Two of eight transient positives from whom serum was available had accompanying transient elevations in anti-H. pylori antibodies. Transiently positive stool ELISAs for H. pylori are common and represent H. pylori in the majority of cases where sequences can be obtained. A not-insignificant percentage of antigen-positive stools, however, may represent other Helicobacter species.

Abstract

An increase in the incidence of esophageal adenocarcinoma has coincided with a decrease in the prevalence of Helicobacter pylori infection. Whether these 2 phenomena are associated is unknown.We conducted a nested case-control study of 128,992 members of an integrated health care system who had participated in a multiphasic health checkup (MHC) during 1964-1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Three randomly chosen control subjects from the MHC cohort were matched to each case subject, on the basis of age at the MHC, sex, race, and the date and site of the MHC. Data on cigarette smoking, alcohol consumption, body mass index (BMI), and education level were obtained at the MHC. Serum samples collected at the MHC were tested for IgG antibodies to H. pylori and to the H. pylori CagA protein.Subjects with H. pylori infections were less likely than uninfected subjects to develop esophageal adenocarcinoma (odds ratio [OR], 0.37 [95% confidence interval (CI), 0.16-0.88]). This significant association was restricted to case subjects and control subjects <50 years old at the MHC (OR, 0.20 [95% CI, 0.06-0.68]). In patients with H. pylori infections, the OR for those who tested positive for IgG antibodies to the CagA protein was similar to that for those who tested negative for it. BMI >/=25 and cigarette smoking were strong independent risk factors for development of esophageal adenocarcinoma.The absence of H. pylori infection, independent of cigarette smoking and BMI, is associated with a markedly increased risk of development of esophageal adenocarcinoma.

Abstract

Helicobacter pylori infection is thought to modify susceptibility to gastroenteritis.Members of northern California households with an index case of gastroenteritis were interviewed regarding recent episodes and tested for H. pylori. Conditional logistic regression was used to evaluate the risk of secondary gastroenteritis within households matched for members with secondary gastroenteritis (cases) and those without symptoms (control subjects). Case and control subjects were also tested for hepatitis A virus (HAV).Of 801 households, 205 (26%) had at least 1 member with secondary gastroenteritis, of which 116 (56%) also included at least 1 member without symptoms (158 case and 285 control subjects). Compared with uninfected members and adjusting for age, those with antibodies to only 1 infection were at a decreased risk of secondary gastroenteritis (odds ratio [OR] for H. pylori infection, 0.25 [95% confidence interval [CI], 0.08-0.82]; OR for HAV, 0.45 [95% CI, 0.23-0.87]). Having antibodies to both H. pylori and HAV did not add to this negative effect (adjusted OR, 0.39 [95% CI, 0.18-0.84]).H. pylori did not increase the risk of gastroenteritis in these households. A strong negative association between H. pylori infection and gastroenteritis is likely explained by prior exposure and immunity to other enteric pathogens.

Abstract

Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice.

Abstract

Helicobacter pylori causes gastric adenocarcinoma; whether treatment of H. pylori infection prevents this cancer remains unknown. In a randomized, double-blind, placebo-controlled trial of H. pylori eradication, we determined whether treatment for H. pylori decreases gastric cancer risk, using preneoplastic conditions as surrogate markers. A total of 248 healthy volunteers (age >40 years) randomly received H. pylori treatment (omeprazole, amoxicillin, clarythromycin; n = 122) or matched placebo (n = 126) for 1 week. Endoscopy was performed at baseline and at 6 weeks and 1 year. Seven biopsies from each endoscopy were reviewed by two pathologists using the revised Sydney classification. Outcome measures were both a consensus "worst biopsy" diagnosis and a weighted index score that incorporated degrees of severity of preneoplasia from all biopsies. We compared change in these outcomes over time between the two treatment groups. H. pylori cure rates for compliant subjects in the treatment arm were 79.2% and 75.7% at 6 weeks and 1 year, respectively. No statistically significant change in the worst biopsy diagnosis was observed from 6 weeks to 1 year between placebo and treated subjects (for improvement/worsening, placebo, 19.4%/10.5%; treatment, 22.5%/8.3%; P = 0.74). Change in index score was favorably greater in treatment compared with placebo subjects (intention-to-treat analysis, P = 0.03); this finding was particularly evident in the antrum. H. pylori eradication gave more favorable gastric histopathologies over 1 year than no treatment. Such incomplete regression suggests but does not prove that eradication of H. pylori decreases cancer risk.

Abstract

Helicobacter pylori infection is usually acquired in childhood, but precise estimates of the age of acquisition are difficult to obtain in young children. Since serial endoscopic biopsies are not feasible in human infants, we examined acquisition of H. pylori infection that is known to occur in socially housed nonhuman primates. By 12 weeks of age, 8 of 20 newborns (40%) were culture positive for H. pylori, and prevalence reached 90% by 1 year of age. Newborns from infected dams were more commonly infected than those from uninfected dams, particularly during the peripartum period, suggesting that close contact during this time may facilitate transmission. Transient infection was uncommon and occurred only after the first positive culture. These results suggest that in a high-prevalence environment, persistent H. pylori infection may be acquired at an earlier age than was previously thought. Since clean, potable water was readily available, contamination of water supply is not essential for widespread infection at an early age in areas where hygiene is otherwise poor. Furthermore, breastfeeding seems to offer little protection, since newborn macaques breastfeed during the first year of life and typically are fully weaned only when another newborn arrives the following spring.

Abstract

Reinfection with any organism is related to the force of infection in the population and on both innate and acquired immunity to infection. Little is yet known about primary immune protection against Helicobacter pylori. Some data suggest that children can be recurrently infected, spontaneously eliminating the organism only to be infected again and again until the organism takes hold. This pattern of recurrent infection is not observed in patients who receive eradication therapy for chronic infection. After eradication of infection, the rate of reinfection is probably slightly lower than the primary infection rate in that age group, suggesting some level of acquired immunity. In developed countries, reinfection of adults in unusual, and recurrence usually represents failure of primary eradication rather than new infection. Some cases of reinfection do occur, however. Given that acquired immunity probably varies little from population to population, reinfections will most likely occur in areas where the force of infection is high, ie, where both the prevalence of infection and the opportunities for transmission are high.

Abstract

C-reactive protein (CRP), Chlamydia pneumonia, Helicobacter pylori, and cytomegalovirus (CMV) have each been associated with atherosclerosis. We assessed how infection and CRP related to risk for subsequent myocardial infarction (MI).Using a nested case-control design, we assessed how these factors independently and jointly affected risk for myocardial infarction (MI). Cases of first MI (N = 121) were identified from among participants in a multiphasic health check-up cohort. Controls without MI (N = 204) were matched to cases by gender, age, race, and date of serum collection. Sera collected at enrollment were tested for antibodies to infection and for CRP.In multivariate analysis (mean follow-up of 5.1 years), CRP was associated with MI only in subjects older than 51 years (p = 0.004). Although H. pylori infection increased risk for MI, this association was modest (OR = 1.90, 95% CI = 0.97-3.71) and was not evident in non-smokers or when adjusted for education. No association between C. pneumoniae or cytomegalovirus and MI was observed, nor was the association between CRP and MI explained by these infections.Elevated CRP is a risk factor for subsequent MI in older individuals. The relationship between Hp and MI may be due to confounding or co-linearity with socioeconomic status.

Abstract

To describe the variation in clinical practice strategies for the treatment of suspected ventilator-associated pneumonia (VAP) in a population of critically ill patients, and to determine whether initial empiric treatment with certain antibiotics, monotherapy vs combination antibiotic therapy, or appropriate vs inappropriate antibiotic therapy is associated with survival, length of hospital stay, or days free of antibiotics.Prospective, observational cohort study.Medical-surgical ICUs of two university-affiliated tertiary medical centers.Between May 1, 1998, and August 1, 2000, we screened 7,030 ICU patients and identified 156 patients with clinically suspected VAP. Patients were followed up until death or discharge from the hospital.The mean age was 62 years, mean APACHE (acute physiology and chronic health evaluation) II score was 14, and mortality was 34%. Combination antibiotic therapy was used in 53% of patients. Piperacillin-tazobactam, fluoroquinolones, vancomycin, cephalosporins, and aminoglycosides were the most commonly employed antibiotics. Initial empiric antibiotics were deemed appropriate in 92% of patients. The predominant organisms isolated from respiratory secretions included Pseudomonas aeruginosa and Staphylococcus aureus. Patients had lower in-hospital mortality rates if their initial treatment regimen included an antipseudomonal penicillin plus beta-lactamase inhibitor (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21 to 0.80; p = 0.009). There was also a strong trend toward reduced mortality rates in patients treated with aminoglycosides (HR, 0.43; 95% CI, 0.16 to 1.11; p = 0.08). Specific antibiotic therapy was not associated with length of hospital stay or days free of antibiotics. Outcomes were similar for patients treated with monotherapy vs combination therapy, and for patients who received initial appropriate vs inappropriate therapy.Patients with clinically suspected VAP who receive initial empiric therapy with antipseudomonal penicillins plus beta-lactamase inhibitors, and possibly aminoglycosides, have lower in-hospital mortality rates when compared with those who are not treated with these antibiotics. These agents should be considered for the initial empiric therapy of VAP.

Abstract

We previously identified viable Helicobacter pylori in stools from asymptomatic hosts. We now report whether a decrease in gastric acidity enhances faecal shedding. Sixteen asymptomatic H. pylori-positive patients underwent two separate days of phosphosoda-induced diarrhoea, both with normal gastric acidity and under hypochlorhydric conditions induced with the H2-blocker cimetidine. Stool samples were collected for culture to determine the presence of viable H. pylori. Five of the 16 patients gave positive cultures with at least one stool from both normal pH and cimetidine-induced hypochlorhydria. Four were negative for all samples with both. Six gave positive stools only after cimetidine treatments, while one gave positive samples with normal pH but not with cimetidine (two-tailed P value, 0.13; McNemar test). These numbers show a trend suggesting that cimetidine-induced hypochlorhydria increases shedding of viable H. pylori.

Abstract

Helicobacter pylori (HP) infection can cause hypochlorhydria, a positive risk factor for Mycobacterium tuberculosis (MTB) infection. This study examined the association between HP and MTB infections among persons attending the Policlinico Peruano Japonés Gastrointestinal Clinic in Lima, Peru. From 23 June 2000 to 18 August 2000, consenting 18-55 year olds who attended the clinic for gastric biopsy gave blood for HP serologic testing, underwent tuberculin skin testing (TST) and completed a social and medical history. Of 128 participating patients, 78 (61%) were TST positive for MTB, and 107 (84%) were infected with HP by serology. Of the patients who were HP positive, 67 (63%) developed positive TST reactions compared to 11 (52%) of 21 HP-seronegative subjects (OR 1.29; 95% CI 0.54-3.11; P = 0.6). There was no association after adjusting for covariates of H. pylori infection (OR 0.78; 95% CI 0.23-2.71; P = 0.7). However, study power was limited by high prevalence of the two infections.

Abstract

The Sydney system recommends sites and numbers of stomach biopsies (mapping) for evaluation of Helicobacter pylori-associated lesions. The diagnostic yield of the recommended mapping technique in populations at high risk for gastric preneoplastic lesions has not been established. We evaluated pathology data from 733 endoscopies performed as part of an intervention study that assessed the effects of H. pylori treatment on preneoplastic conditions. Two pathologists assessed whether the mapping sequence of the 7 biopsy specimens obtained during each endoscopy was correctly followed and graded the specimens using the Sydney classification for gastritis. If the mapping sequence was followed, then we evaluated whether the amount of information obtained from 3 biopsy samples approximated that obtained from 5 and 7 biopsy samples. The mapping sequence was followed in only 239 (33%) endoscopies, indicating that experienced endoscopists can inadvertently misidentify sites in the stomach when obtaining specimens. When data from 7 specimens were used, H. pylori was found in 205 endoscopies, atrophy in 152, metaplasia in 135, and dysplasia in 22. When data from 3 specimens were used, the sensitivity was 99% for presence of H. pylori, 82% for atrophy and metaplasia, and 81% for dysplasia. When data from 5 specimens were used, the sensitivity was 100% for H. pylori, 96% for atrophy, and 95% for metaplasia and dysplasia. Although site-specific biopsy mapping is difficult in practice, the recommendations of the Sydney system as to the location and number of gastric biopsy specimens can adequately identify significant gastric histopathology.

Abstract

Most infections occur during childhood, but the health effects of childhood infection are poorly understood. We investigated whether growth decreases in the 2 months after acute seroconversion.We performed a nested case-control study among children 6 months to 12 years of age in a community on the outskirts of Lima, Peru. Health interviews were completed daily. Anthropometric measurements were taken monthly. Sera were collected every 4 months and tested for immunoglobulin G. Two-month height and weight gains of seroconverters were compared with gains of sex, age, and size-matched seronegative controls.In the 2 months after infection, 26 seroconverters gained a median of 24% less weight than 26 matched controls (interquartile range, 63% less to 21% more). In multivariate analysis, infection attenuated weight gain only among children aged 2 years or older. This decrease was not explained by increased diarrhea.seroconversion is associated with a slowing of weight gain in children aged 2 years or older. Reasons for this finding merit additional study.

Abstract

Helicobacter pylori causes gastric adenocarcinoma. We assessed the success of H. pylori eradication therapy in a medically underserved population in Chiapas, Mexico, that is at high risk for gastric cancer risk.Healthy volunteers with both antibodies to CagA and gastrin levels > or = 25 ng/ml were randomly assigned to receive either a combination of omeprazole, amoxicillin, and clarithromycin or matched placebo for 1 wk. Endoscopy with seven biopsies was performed at baseline, at 6 wk, and 1 yr after treatment. Treatment success was defined as loss of H. pylori by histological analysis. Cure was assessed using change in serology based on the standardized absorbance of a H. pylori ELISA.H. pylori eradication rates were high (intent-to-treat analysis: 76.3% [95% CI = 68.7-84.0%] after 6 wk and 76.1% [95% CI = 67.7-84.6%] after 1 yr; per protocol analysis: 77.8% [95% CI = 70.1-85.4%] after 6 wk and 75.2% [95% CI = 66.5-84.0%] after 1 yr). Nine subjects on active treatment and one subject on placebo who were without H. pylori at 6 wk were infected at 1 yr (recurrence rates 10.7% and 33.3%, respectively, p = 0.31). Median changes in standardized absorbance at 1 yr were 47% and 1% for successfully and unsuccessfully treated patients, respectively. A 10% decline in standardized absorbance after 1 yr had 84% sensitivity and 100% specificity for H. pylori eradication.Even with a short course of treatment against H. pylori, a high rate of eradication rate can be achieved in populations at high risk for stomach cancer. Serum antibodies are useful in assessing efficacy of therapy.

Abstract

Stomach cancer is the second cause of death in Mexico in patients with malignant tumors. This disease represents a public health problem. A strong association has been described between chronic infection with Helicobacter pylori and gastric cancer. This malignancy is preceded by a series of preneoplastic conditions, including chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia. The objective of this study was to establish the prevalence of preneoplastic conditions associated with infection of Helicobacter pylori in the state of Chiapas and its eradication with antibiotics. Persons infected with Helicobacter pylori and with CAG were identified by serology against CagA protein and serologic levels of gastrin. An endoscopy with biopsy was performed at the beginning of the study, and at 6 weeks and 1 year thereafter. A total of 281 people were enrolled and randomly assigned to treatment or placebo group. CAG was found in 59%, IM in 51%, and dysplasia in 13%. In intent-to-treat and per-protocol analysis, Helicobacter pylori was eliminated in 70 and 76%, respectively. These results indicate high frequency of preneoplastic conditions associated with Helicobacter pylori and an excellent eradication rate. They also offer a possible alternative for preventing gastric cancer.

Abstract

Helicobacter pylori is uniquely adapted to colonize the human stomach. Infection leads to a range of subclinical and clinical outcomes that depend on properties of the infecting strain, the host, and the environment. Eradication therapy is indicated for infected persons who develop peptic ulcer disease or gastric lymphoma or who are beginning long-term treatment with nonsteroidal anti-inflammatory drugs. However, treatment may worsen gastroesophageal reflux disease and increase the risk of esophageal cancer. H. pylori infections can be diagnosed noninvasively and can be eradicated with approximately 85% success by a variety of multidrug, 7-14-day regimens. Unfortunately, antibiotic resistance is affecting treatment effectiveness in the United States and abroad. A more complete understanding of the variation in H. pylori pathogenesis should lead to clearer recommendations about treatment for infected persons who have neither peptic ulcer disease nor gastric lymphoma.

Abstract

Gastric acid is an important defence against enteric infection. Studies investigating the relationship between hypochlorhydria and enteric infections or gastric malignancy have been limited by difficulties in the non-invasive measurement of gastric acidity.To develop a blood test for hypochlorhydria based on the quininium resin test.Quininium resin dissociates to liberate free quinine at pH

Abstract

Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.

Abstract

No dyspepsia-specific questionnaire currently exists in Spanish. The Spanish Language Dyspepsia Questionnaire (SLDQ) was developed based on Rome dyspepsia criteria, other questionnaires, and common symptoms. Self-reported normal and dyspeptic volunteers (N = 63) in Chiapas, Mexico, participated in a validation study. We assessed intra- and interrater reliability by test-retest studies and established validity by both correlation to the Short Form-36 (SF-36) and comparison of scores between normals and dyspeptics. The total SLDQ score showed a wide distribution (range 0-78, mean 23.7 +/- 21.9). Internal reliability of the SLDQ was high (Cronbach's a = 0.93). Intra- and interrater reliability were excellent (scores from the first and second interviews not statistically different; P = 0.94; intraclass correlation coefficient = 0.96). SLDQ scales correlated appropriately with the SF-36. The SLDQ distinguished self-classified normals from dyspeptics (P < 0.001). The SLDQ fills the unmet need for a valid, reproducible, and multidimensional Spanish-language instrument to measure dyspepsia. Additionally, we have made suggestions for the development of symptom-quantifying questionnaires.

Abstract

Helicobacter pylori vaccines, which have been suggested as promising interventions to control infection, are under development. We sought to quantify the potential population impact of a prophylactic H. pylori vaccine.We developed a mathematical model that compartmentalized the population according to age, infection status and clinical state. A proportion of individuals was assumed to acquire infection and develop gastritis, duodenal ulcer (DU), chronic atrophic gastritis and gastric cancer (GC). We first simulated the model without vaccine intervention, to obtain estimates of H. pylori prevalence, and GC and DU incidences based on intrinsic dynamics. We then incorporated a prophylactic vaccine (80% efficacy, lifetime protection, 80% coverage) targeting all infants. We tested vaccination programs over unlimited as well as limited time spans. Analyses were performed for the US, Japan and a prototypical developing country.In the US, our model predicted a decrease in H. pylori prevalence from 12.0% in 2010 to 4.2% in 2100 without intervention. With 10 years of vaccination beginning in 2010, prevalence would decrease to 0.7% by year 2100. In the same period, incidence of H. pylori-attributable GC would decrease from 4.5 to 0.4 per 100,000 with vaccine (compared to 1.3 per 100,000 without vaccine). Incidence of H. pylori-attributable DU would decrease from 33.3 to 2.5 per 100,000 with vaccine (compared to 12.2 per 100,000 without vaccine). In Japan, incidence of H. pylori-attributable GC would decrease from 17.6 to 1.0 per 100,000 after 10 years of vaccination (compared to 3.0 per 100,000 without vaccine). In a prototypical developing country, after 10 years of vaccination, H. pylori-attributable GC would decrease from 31.8 to 22.5 per 100,000 by 2090, returning to the original level by mid-2100s. Under continuous vaccination, it would decrease to 5.8 per 100,000 by 2100.In the US and Japan, a 10-year vaccination program would confer almost the same reduction in H. pylori and associated diseases as a vaccination effort that extends beyond 10 years. In developing countries, a continuous vaccination effort would be required to eliminate the pathogen and its associated diseases.

Abstract

We sought to determine the infectious dose of Helicobacter pylori during primary and secondary infection in the rhesus monkey and to determine whether preinoculation acid suppression is necessary to produce colonization. Mixed inoculation with three human-derived strains showed that H. pylori J166 is particularly adapted to colonization of rhesus monkeys, since it outcompeted two other strains. The minimum infectious dose of H. pylori J166 was 10(4) bacteria in specific-pathogen (H. pylori)-free monkeys. Rechallenge of these monkeys after antibiotic therapy was characterized by a 10- to 100-fold decrease in bacterial load compared to primary infection, but with little change in the infectious dose. Acid suppression prior to inoculation was not necessary for colonization to occur. These results provide a basis for future animal experiments using more ecologically relevant conditions of inoculation and suggest that reduction in bacterial load rather than complete protection may be a more realistic goal for H. pylori vaccination.

Abstract

Cohort and case-crossover studies were conducted to evaluate whether new Helicobacter pylori infections are followed by increased diarrhea.Participants were 6-month-old to 12-year-old shantytown residents living near Lima, Peru. Baseline data were collected from community households. Health interviews were completed daily, and sera, drawn every 4 months, were tested for H pylori immunoglobulin G. Diarrhea rates among newly H pylori-infected (seroconverting) children were compared with rates among persistently uninfected and infected children using cohort and case-crossover analyses.Sera were obtained from 345 children from January 1, 1995, through September 1, 1997. H pylori incidence was 12% per year (36 H pylori infections in 109 866 seronegative days). In adjusted cohort analyses, seroconverters had more diarrhea days (rate ratio: 2.0; 95% confidence interval: 1.6-2.4), episodes, and sick days in the year after infection than did uninfected children; and more diarrhea days and sick days than did persistently infected children. This effect was strongest in the first 2 months. Case-crossover analyses supported these findings.Preventing H pylori infection may help reduce pediatric diarrheal disease.

Abstract

Gastric cancer is the second most common cause of cancer death in the world. Helicobacter pylori infection is now a well-accepted cause of this malignancy; in some parts of the world, up to eighty percent of all gastric cancers are at least in part caused by H. pylori infection. H. pylori infection typically starts in childhood as an inflammatory process in the stomach. The changes in the gastric microenvironment facilitate gastric cancer over time. Among infected individuals, genotype of H. pylori, coincident environmental exposures, and genetic factors of host seem to play roles in determining who will get gastric cancer and who will not. Unfortunately, it remains unknown whether treatment of H. pylori prevents gastric cancer. Thus, screening for H. pylori to prevent cancer is not yet widely recommended. Some consensus groups, however, have recommended screening for and treating H. pylori infection in individuals with family histories of gastric malignancy. In high-risk countries, screening programs for early gastric cancer itself may improve therapeutic outcome for this highly lethal disease.

Abstract

Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

Abstract

Atrophy and intestinal metaplasia (IM) are preneoplastic gastric lesions associated with Helicobacter pylori infection. Atrophy and IM are usually found together; however, the association between increasing degrees of severity of both atrophy and IM has not been evaluated completely. Two pathologists graded atrophy and IM using the visual analog scale of the Sydney classification in gastric biopsies from 368 H pylori-infected patients. Extent of IM also included determining the number of specimens affected. We then correlated the degree of atrophy with the degree and number of specimens affected with IM by calculating relative risks (RR) and 95% confidence intervals (95% CI). The mean number of biopsies examined from each patient was 6.5. Atrophy and IM were found more frequently in the antrum (85% and 75% of biopsies, respectively). One hundred thirty-eight patients had a combination of atrophy and IM, 48 had IM only, and 89 had atrophy only. Fifty-three subjects had mild atrophy and IM (RR = 1.57; 95% CI 1.2-2.1), 69 had moderate atrophy and IM (RR = 1.86; 95% CI 1.9-2.4), and 16 had marked atrophy and IM (RR = 2.47; 95% CI 1.8-3.3). The median number of biopsy specimens with IM increased from 0 in subjects with no atrophy to 3 in subjects with severe atrophy. The degree of IM correlated with the degree of atrophy; the median degree was 0.6 in subjects with no atrophy and increased to 2.32 in those with severe atrophy. Our data suggest that higher degrees of IM in an individual specimen and increasing number of specimens with IM are associated with moderate or severe degrees of atrophy.

Abstract

Epidemiology of gastric adenocarcinoma suggests that intestinal-type and diffuse-type cancers develop through distinct causal pathways. To examine the differences in risk factors and molecular changes between the histological types, reliable data on histological typing are essential. We evaluated the concordance between two pathologists in assessment of 95 gastric adenocarcinomas for Laurén classification and tumor grade. Two pathologists, each blinded to the other's assessment, reviewed H&E-stained slides of gastric tumor. The responses of the two pathologists for histological type were considered as concordant if they fell on one of the three categories (intestinal type, diffuse type, or other). Tumor grade was classified into three categories (well, moderately, or poorly differentiated). The pathologists agreed on the classification of histological type for 71 of 92 (77%) tumors. Kappa coefficient was 0.59 (95% confidence interval, 0.44-0.73). Concordance for tumor grade was 87%, with a kappa coefficient of 0.72 (95% confidence interval, 0.57-0.87). Both observed concordance and kappa coefficient for histological type and tumor grade were similar across three calendar periods of study. Interobserver agreement was virtually identical between tumors with biopsy specimens only and those with surgical specimens. Although the level of disagreement for histological type observed in this study is comparable with that in other studies, the resulting misclassification would lead to the reduction in observed differences in prevalence and odds ratio estimates between two histological types.

Abstract

Results obtained with commercial testing kits for immunoglobulin M Toxoplasma antibodies may be inaccurate or may be inaccurately interpreted, which may influence whether a woman decides to terminate the pregnancy. This study was undertaken to determine whether confirmatory testing at a reference laboratory and communication of the results and an expert interpretation to the patient's physician would affect the rate of induced abortions among pregnant women with positive results of testing for immunoglobulin M Toxoplasma antibodies in outside laboratories.This was a retrospective cohort study of 811 consecutive pregnant women for whom the toxoplasma serologic profile was performed at a reference laboratory. Almost all the patients had been informed by their physicians that a result of a test for immunoglobulin M Toxoplasma antibodies performed in an outside laboratory was positive. Women were separated into those with a toxoplasma serologic profile result suggestive of a recently acquired infection (group 1) and those with a result suggestive of an infection acquired in the more distant past (group 2). Physician reports of induced abortions were used to determine rates of induced abortion in groups 1 and 2.Of the 811 women 321 (39.6%) were considered likely to have a recent infection (group 1) and 490 (60.4%) were considered likely to have a past infection (group 2). Physicians reported pregnancy outcomes for 433 (53.4%) of 811 women (65.1% and 45.7% in groups 1 and 2, respectively). Whereas 36 of 209 women in group 1 (17.2%) terminated the pregnancy, only 1 of 224 women in group 2 (0.4%) chose abortion (P

Abstract

To assess the benefits of intervention programs against Helicobacter pylori infection, we estimated the baseline curves of its incidence and prevalence. We developed a mathematical (compartmental) model of the intrinsic dynamics of H. pylori, which represents the natural history of infection and disease progression. Our model divided the population according to age, infection status, and clinical state. Case-patients were followed from birth to death. A proportion of the population acquired H. pylori infection and became ill with gastritis, duodenal ulcer, chronic atrophic gastritis, or gastric cancer. We simulated the change in transmissibility consistent with the incidence of gastric cancer and duodenal ulcer over time, as well as current H. pylori prevalence. In the United States, transmissibility of H. pylori has decreased to values so low that, should this trend continue, the organism will disappear from the population without targeted intervention; this process, however, will take more than a century.

Abstract

In a cross-sectional study of the 1991 Peruvian cholera epidemic, Vibrio cholerae O1 infection was associated with Helicobacter pylori infection, particularly in young children. These data support the hypothesis that hypochlorhydria induced by H. pylori is important in the pathogenesis of diarrhoeal disease.

Abstract

The Sydney classification for gastritis provides guidelines for histological grading of gastric biopsies. In an ongoing study of gastric preneoplastic lesions in Chiapas, Mexico, 7 biopsies from 150 patients (4 from the antrum and 3 from the body) were obtained during endoscopy and studied histologically. The first 74 endoscopy specimens were read independently by 2 general surgical pathologists. We assessed diagnostic concordance using kappa statistics. The 2 pathologists then jointly reviewed biopsies about which they had disagreed to reach a final diagnosis. A second group of 76 endoscopies was subsequently evaluated independently by the 2 pathologists, and concordance was again assessed. In the first group of biopsies, we found low concordance rates (Heliobacter pylori 0.59, acute inflammation 0.22, intestinal metaplasia 0.60, and atrophy 0.04). In the second group, of independently reviewed cases, there was better concordance (H pylori 0.77, acute inflammation 0.50, intestinal metaplasia 0.70, and atrophy 0.64). We presumed that use of the Sydney classification would result in minimal interpretational differences achieving ideal kappas greater than 0.80. Because pathology results are based on subjective interpretation of this classification, complete diagnostic agreement is practically impossible. Concordance by general surgical pathologists after joint review of cases was similar to that obtained by gastrointestinal pathologists.

Abstract

Prophylactic vaccination has been suggested as a better strategy than antibiotics to control Helicobacter pylori infection. We evaluated the cost-effectiveness (CE) of H. pylori vaccine development and use in the United States and developing countries, using a method developed by the Institute of Medicine (IOM).The IOM model includes costs of vaccine development, vaccination program, and averted medical treatments; morbidity and mortality prevented; expected efficacy and use; and proportion of disease that is vaccine-preventable. The model employs infant mortality equivalence (IME) to estimate disease burden; with IME, the societal cost of infection-related morbidity is expressed as equivalent to a specific rate of infant deaths. We tested model assumptions by univariate sensitivity analyses.In the United States, H. pylori vaccine would save 1,176 IME and would cost $58.71 million (1997 dollars) annually, yielding a CE ratio of $49,932 per IME; the health benefits would exceed all IOM-studied vaccines, even when efficacy dropped to 55%. H. pylori vaccine could be cost-saving if priced at less than $60 per course. In developing countries, H. pylori vaccine would rank unfavorably both in terms of health benefits (33,518 IME) and costs ($5,254 million). None of the changes in assumptions improved significantly the H. pylori vaccine's ranking relative to other IOM-studied vaccines.Compared to other vaccines evaluated in the IOM study, H. pylori vaccine warrants public resource allocation for accelerated development and use in the United States but not for use in developing countries.

Abstract

Stored sera from a cohort of 2397 male factory workers in Harare, Zimbabwe, were screened for herpes simplex virus type 2 (HSV-2)-specific antibodies, to estimate the prevalence and incidence of genital herpes infection and to assess the relation between HSV-2 and human immunodeficiency virus (HIV) acquisition. The prevalence of HSV-2 at enrollment was 39.8%. Correlates of HSV-2 seropositivity were HIV seropositivity, marital status, history of sexually transmitted disease (STD), older age, and higher income. The incidence of HSV-2 seroconversion during follow-up was 6.2/100 person-years. Correlates of HSV-2 seroconversion were enrollment while HIV-positive or seroconversion during follow-up, reported genital ulcer, history of STD, and number of sex partners. No evidence was found that HSV-2 infection was more likely to precede HIV or vice versa. HSV-2 and HIV seropositivity are strong markers for high-risk sexual behavior. Improved interventions targeted to populations in which the incidence of either viral infection is high are needed.

Abstract

Strains of Helicobacter pylori that express the CagA protein are associated with a threefold increased gastric cancer risk as compared to H. pylori strains that do not express CagA. Screening and treatment only for CagA antibodies should target those individuals at highest gastric cancer risk while reducing the number of patients requiring antibiotics. We compared the costs and benefits of screening asymptomatic 50-year-old individuals for CagA, screening for all H. pylori strains, and no screening, both in the United States and abroad.We employed Markov cost-effectiveness analysis using data from randomized, case-control, and cohort studies.In the United States, CagA screening would result in 1.5 million fewer antibiotic treatments but would prevent 1,400 fewer gastric cancers than would screening for all H. pylori. The incremental cost-effectiveness of CagA screening is $23,900 per life-year gained; for H. pylori screening, it is $25,100. Screening in countries with epidemiological characteristics similar to those of Colombia, Finland, and Japan costs less than $5,000 per life-year gained, and the difference between CagA and H. pylori screening is smaller than that in the United States.Screening only for CagA-positive H. pylori is not substantially better than is screening for all H. pylori, either in the United States nor abroad. Screening is substantially more cost-effective outside the United States. Whether population screening is justified, however, is uncertain pending conclusive data regarding the reduction in gastric cancer risk from antibiotics.

Abstract

Isolated for the first time in 1982 from human gastric biopsy, Helicobacter pylori is responsible for gastritis, peptic ulcer, and gastric cancer. A pathogenicity island acquired by horizontal transfer, coding for a type IV secretion system, is a major determinant of virulence. The infection is now treated with antibiotics, and vaccines are in preparation. The geographic distribution suggests coevolution of man and Helicobacter pylori.

Abstract

Development of the rhesus monkey model of Helicobacter pylori has been hampered by problems with serodetection and by the difficulty of identifying specific-pathogen (Helicobacter)-free animals. Our purpose was to determine whether detection could be improved and to determine if pathogen-free monkeys could be derived by nursery rearing.An enzyme-linked immunoabsorbent assay (ELISA) and a [14C]urea breath test were compared to endoscopy to determine H. pylori infection status in rhesus macaques; 18 animals were hand raised in the nursery to determine whether pathogen-free animals could be selected.Helicobacter pylori infection was common in colony-raised young rhesus monkeys and was nearly universal by adulthood. Serodetection, using antigen from rhesus-derived H. pylori strains, was 95% sensitive and 94% specific. The [14C]urea breath test was 96% sensitive and 88% specific for detection of chronic Helicobacter infection in rhesus monkeys. Segregation of newborn animals within the first 24 h of life was a reliable method to obtain pathogen-free rhesus monkeys.Isolation of specific-pathogen-free animals, together with better detection methods, may improve the value of the rhesus monkey model for the study of H. pylori pathogenesis, immune response, and vaccine development.

Abstract

In Chiapas, Mexico, diarrheal disease causes the majority of all deaths in children under the age of five. Treatment of childhood diarrhea may be influenced by local beliefs and cultural practices. Few studies have attempted to quantitatively evaluate health seeking behavior (HSB) for diarrheal diseases in indigenous communities, while controlling for potential confounding factors such as parental education or socioeconomic status. A rapid ethnographic survey was conducted in Nabenchauc, Chiapas, to determine hypothetical HSB patterns for each of four major types of childhood diarrhea. Additionally, we examined the actual HSB for the last episode of childhood diarrheal illness within the household. One hundred households participated in the survey; 94 households with children < 5 years old reported a mean of 1.9 diarrheal episodes during the preceding month. Households reported using a mean of 1.3 types of in-home remedies. Oral rehydration therapy (ORT) was used in <2% of the 368 HSB patterns elicited for the four types of diarrhea. HSB patterns utilized an eclectic combination of traditional, allopathic, local and distant health care options. A mean of 2.5 outside-the-home health care options were reported for each diarrheal type; the local grocery store was reported in 245 (67%) of the hypothetical HSB patterns and as a first option in 199 (54%). Maternal and/or paternal education had little impact on hypothetical HSB. Households with lower SES were more likely to report using local grocery stores as a first option and were less likely to use options outside the village. The rapid ethnographic survey approach allows for assessment of changes in the approach to health care option utilization in cultures incorporating new health care paradigms. Public health interventions targeting local stores may lead to increased use of ORT, thereby potentially reducing early morbidity and mortality due to childhood diarrhea.

Abstract

Gastrin is a putative promoter of colorectal carcinomas. The aim of this study was to evaluate the temporal relationship between gastrinemia and development of colorectal malignancy.We conducted a nested case-control study among 128,992 subscribers to a health maintenance program who had participated in a multiphasic health checkup between 1964 and 1969. Serum had been frozen since the checkup and the cohort followed up for cancer. Of 1881 incident colorectal carcinoma cases, 250 were randomly selected; 1 control without cancer was matched to each case by age, sex, education, and date of serum collection. Stored sera were tested for Helicobacter pylori immunoglobulin G and for gastrin and glycine-extended gastrin.Verified cases included 166 colon cancers, 58 rectal cancers, and 9 with cancer in both locations. A mean of 15.3 years had elapsed between serum collection and diagnosis of cancer. Median gastrin levels were similar in cases and controls (41.7 vs. 40.7 pg/mL). However, a gastrin level above normal was associated with increased risk for colorectal malignancy (odds ratio, 3.9; 95% confidence interval, 1.5-9.8). If this association is causal, 8.6% of colorectal cancers could be attributed to high serum gastrin level.Hypergastrinemia is associated with an increased risk of colorectal carcinoma.

Abstract

Helicobacter pylori infection causes peptic ulcer disease, gastric adenocarcinoma, gastric lymphoma, and probably nonulcer dyspepsia. Although the prevalence of infection is declining over time, the organism still infects approximately one half of the world's population. Only a minority will ever suffer serious consequences from their infection. This article reviews current knowledge about H. pylori and presents some of the dilemmas surrounding clinical and public health approaches to this widespread pathogen.

Abstract

Infection with Helicobacter pylori increases the risk for gastric non-Hodgkin's lymphoma (GNHL). Strains that express CagA protein are thought to be particularly virulent. It was determined whether CagA+ H. pylori infection increased the risk for GNHL more than CagA infection. Thirty-two cases and 130 controls previously tested for H. pylori antibodies were tested for CagA antibodies by ELISA. The risk for GNHL was compared among CagA+, CagA-, and uninfected persons by use of conditional logistic regression. CagA+ subjects had 8.2 times the risk for GNHL than uninfected persons (95% confidence interval [CI], 2.5-26.7). CagA- subjects had 4.4 times the risk for GNHL than uninfected persons (95% CI, 1.2-16.5). Among infected subjects only, CagA+ infection was not associated with significantly increased risk for GNHL when compared with CagA- infection (odds ratio, 2.1; 95% CI, 0.8-5.4). This study does not support a major role for CagA in lymphomagenesis.

Abstract

Phytoestrogens include several classes of chemical compounds (i.e., isoflavones, coumestans, and lignans) which are structurally similar to endogenous estrogens. In biological systems, they have both estrogenic and antiestrogenic effects and may reduce the risk of developing certain types of hormonally related diseases. However, little information is available on population differences in exposure to phytoestrogens. To examine racial/ethnic differences in urinary phytoestrogen levels, 50 young women (ages 20-40 years) were randomly selected from participants in a previous epidemiological study in which 24-h urine specimens and a dietary assessment were obtained. Subjects were members of the Kaiser Permanente Medical Care Program of northern California. Selection was stratified on race/ethnicity. Urinary levels of seven phytoestrogens were measured using high-performance liquid chromatography-mass spectrometry. Substantial variation in phytoestrogen levels was observed and racial/ethnic differences are described. The highest levels of coumestrol and the lignans were observed in white women and the lowest levels in Latina and African American women. Genistein levels, however, were highest in Latina women; other isoflavone levels did not differ significantly by race/ethnicity.

Abstract

Helicobacter pylori is categorized into two phenotypes on the basis of the presence or absence of the CagA protein. CagA protein-positive H. pylori are more closely associated with peptic ulcer disease and cancer. Whether CagA-positive strains are similarly represented among racial or ethnic groups in northern California was investigated. Sera from 152 H. pylori-infected healthy young adults were tested by ELISA for IgG against CagA. CagA antibodies were detected in 79.4% of blacks, 63.8% of Hispanics, and 50% of whites. After adjusting for demographic factors, blacks had significantly more infections with CagA-positive H. pylori than did whites (odds ratio [OR] = 5.0; 95% confidence interval [CI] = 1.6-15.3) or Hispanics (OR = 5.5, 95% CI = 1.9-16.0). Also, there was a higher prevalence of CagA in persons born in developing countries than in persons born in industrialized nations (OR = 3.5, 95% CI = 1.3-9.4). This suggests either a genetic predisposition of racial or ethnic groups to infection with particular H. pylori phenotypes or transmission of H. pylori within relatively segregated population groups.

Abstract

It is not known why some people with Helicobacter pylori infection develop gastric cancer whereas others do not. Whether the CagA phenotype of H pylori infection affected risk for cancer independently of other posited risk factors was evaluated.242 persons who participated in a previous nested case-control study of gastric cancer. 179 (90 cases and 89 controls) were infected with H pylori as determined by enzyme linked immunosorbent assay (ELISA) in serum and 63 (13 cases and 50 controls) were uninfected.Serum samples from cases and controls, obtained a mean of 14.2 years before diagnosis of cancer in the cases, were tested by ELISA for IgG antibodies against the CagA gene product of H pylori. They had previously been tested for pepsinogen I. Using logistic regression analysis, risk for cancer was compared among infected persons with CagA antibodies, infected persons without CagA antibodies, and uninfected persons.Subjects infected with H pylori who had CagA antibodies were 5.8-fold more likely than uninfected subjects to develop gastric cancer (95% confidence interval (95% CI) = 2.6-13.0). This was true for both intestinal (odds ratio (OR) 5.1, 95% CI = 2.1-12.2) and diffuse type (OR 10.1, 95% CI = 2.2-47.4) cancers. By contrast, H pylori infected subjects without CagA antibodies were only slightly, and not significantly, at increased risk for cancer (OR 2.2, 95% CI = 0.9-5.4) and any possible association was restricted to diffuse type carcinoma (OR 9.0, 95% CI = 1.2-65.8). Pepsinogen 1 < 50 ng/ml significantly increased risk for both cancer types in H pylori infected persons and lessened the magnitude of association between CagA and cancer. Educational attainment, cigarette smoking, and ABO blood group were not associated with malignancy.When compared with uninfected subjects, persons infected with CagA positive H pylori are at considerably increased risk of gastric cancer. CagA negative H pylori are less strongly linked to malignancy and may only be associated with diffuse type disease.

Abstract

It is unknown whether eradication of Helicobacter pylori infection prevents development of gastric adenocarcinoma. To determine whether screening and treatment trials are warranted, we conducted a cost-effectiveness analysis to estimate the costs and benefits associated with screening for H pylori at age 50 and treating those individuals infected with antibiotics.We compared two interventions: (1) screen for H pylori and treat those with a positive test, and (2) do not screen and do not treat. Estimates of risks and costs were obtained by review of published reports. Since the efficacy of H pylori therapy in cancer prevention is unknown, we did sensitivity analyses, varying this estimate widely. In our base-case analysis, we assumed that H pylori treatment prevented 30% of attributable gastric cancers.In the base-case analysis, 11,646,000 persons in the US would be screened and 4,658,400 treated, at a cost of $996 million. Cost-effectiveness was $25,000 per year of life saved. Cost-effectiveness was sensitive to the efficacy of the cancer prevention strategy. At low efficacy rates (< 10%), the screening programme was more expensive (> $75,000 per year of life saved). In a high-risk group such as Japanese-Americans, however, screening and treatment required less than $50,000 per year of life saved, even at 5% treatment efficacy.Screening and treatment for H pylori infection is potentially cost-effective in the prevention of gastric cancer, particularly in high-risk populations. Cancer prevention trials are strongly recommended.

Abstract

The incidence of gastric non-Hodgkin's lymphoma (NHL) is increasing in the United States. However, little is known about the etiology of the disease. Some studies have shown an association between gastric NHL and Helicobacter pylori. No study has specifically delineated demographic features that distinguish gastric NHL patients from nongastric NHL patients.To obtain information about the differences between gastric and nongastric NHL patients, we conducted a hospital chart review study. We examined charts of all 25 cases of primary gastric NHL, as well as charts of 75 randomly selected nongastric NHL patients as controls. All patients were seen in the Division of Oncology at Stanford University Medical Center from 1972 to 1991. Demographic information was tabulated, and differences between the cases and controls were noted. The identified risk factors were determined by both univariate and logistic regression analyses.There was no difference between gastric NHL cases and nongastric controls with respect to age, gender, race, and family history of any cancer. However, in logistical regression, persons with gastric NHL were more likely than those with other forms of NHL to be born outside the United States (odds ratio = 12.8; 95% confidence interval = 2.9-56.0) and also to have a family history of stomach cancer (odds ratio = 18.4; 95% confidence interval 2.1-160.1).Gastric NHL is more likely than NHL at other sites to occur in persons with a family history of gastric cancer or in those born in developing countries. This epidemiological pattern supports the identified role of H. pylori in the development of gastric lymphoma.

Abstract

Helicobacter pylori infection is now widely recognized as a cause of stomach cancer. We assessed trends in H. pylori infection in Japan, a population with high rates of gastric malignancy.Using an enzyme-linked immunosorbent assay (ELISA), we tested sera collected between 1980 and 1993 from Tokyo University Hospital patients for anti-H. pylori IgG. Patients ranged in age from 0 to 94 years. Helicobacter pylori prevalence was then assessed for age and/or birth cohort effects.Of 1207 sera, 470 (38.9%) were positive for H. pylori IgG. By univariate analysis, both older age and birth in an earlier decade were associated with an increased risk of infection. Age-specific prevalence of H. pylori by birth cohort suggested increases in infection during the decades from 1900 to 1959, and age-specific decreases since 1960. In multivariate analysis, H. pylori infection increased with age and was most prevalent among those born in the 1940s and 1950s.Relative to other birth cohorts, people born in the 1940s and 1950s have a higher prevalence of H. pylori. This increased prevalence of infection among those born in wartime Japan likely attests to the impact of compromised living conditions on acquisition of H. pylori, and may portend continued high rates of gastric cancer in forthcoming years.

Abstract

Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Helicobacter pylori infection. H. pylori has been epidemiologically linked to adenocarcinoma of the distal stomach by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds. H. pylori is the first bacterium to be termed a definite cause of cancer in humans by the International Agency for Research on Cancer. Mutagenic bacterial metabolites are also suspected to increase risk for cancer. This model is best exemplified in colon cancer. Bile salt metabolites increase colonic cell proliferation. Exogenous compounds such as rutin may be metabolized into mutagens by resident colonic flora. Moreover, Bacteroides species can produce fecapentaenes, potent in vitro mutagens, in relatively high concentrations. In vivo data on human carcinogenesis by bacterial metabolites, however, are inconsistent. Local bacterial infections may also predispose to nonnodal lymphomas, although the mechanisms for this are unknown. Gastric lymphomas and immunoproliferative small intestinal disease have been most strongly linked to underlying bacterial infection. Because bacterial infections can be cured with antibiotics, identification of bacterial causes of malignancy could have important implications for cancer prevention.

Abstract

Diseases associated with Helicobacter pylori infection, such as peptic ulcer disease and gastric cancer, afflict men more frequently than women. No study, however, has demonstrated any difference in sex-specific rates of H. pylori infection. In a healthy population undergoing multiphasic health evaluations in 1992-1993 as members of the Kaiser Permanente Medical Care Program of Northern California, adults aged 20-39 years were screened for antibodies to H. pylori infection using a serum enzyme-linked immunosorbent assay and were surveyed with regard to their demographic characteristics and health practices. Among 556 African-American, Hispanic, and white men and women, male sex was a significant risk factor for infection. Other risk factors included African-American race and Hispanic ethnicity, increasing age, living with children, birth in a developing country, and lower levels of income and education. Men consistently had a higher prevalence of antibodies across all strata of race/ethnicity, age, education, and income, and in multivariate analysis male sex remained significantly associated with infection (odds ratio = 2.0, 95% confidence interval 1.2-3.1). African-American race, Hispanic ethnicity, increasing age, lower levels of education, and birth in a developing country were also associated with infection in multivariate analysis. Data from previously reported seroprevalence studies support a tendency for men to have a higher risk of infection. The higher prevalence of infection among young males as observed in Northern California may account in part for the increased incidence of H. pylori-related diseases among men in later decades of life.

Abstract

While the H1-d flagellar serotype of Salmonella typhi has been found worldwide, the H1-j serotype occurs only in Indonesia. A cross-sectional survey in Indonesia compared epidemiologic, clinical, and pathogenetic characteristics of these two serotypes. S. typhi isolates were collected from patients with acute typhoid fever in four Indonesian cities. Flagellar serotype was determined by polymerase chain reaction amplification of the fliC locus of the flg gene. Of 321 isolates, 51 (15.9%) were H1-j. Patients with H1-j infection were older than those with H1-d (P < .001). Among 30 patients with known clinical outcomes, H1-j infection was associated with milder clinical illness than H1-d (P = .06). In vitro, H1-j isolates were both less motile on semi-solid agar plates (P = .004) and less invasive of HEp-2 cells (P = .002) than H1-d isolates. The association of decreased severity of illness with decreased motility and invasiveness suggests that flagellar properties are a component of S. typhi's virulence.

Abstract

Acute Helicobacter pylori infection invariably passes undetected. Consequently, the incidence of infection has been determined indirectly from epidemiological studies. In adults of industrialized countries, an estimated 0.5% of the susceptible population becomes infected each year. This incidence has been decreasing over time. Thus, adults who currently harbour the organism are more likely to have been infected in childhood than adulthood. The incidence of H. pylori infection continues to be high (between 3% and 10% per year) in developing countries. Throughout the world, incidence of H. pylori infection appears to be higher in children than in adults, possibly due to lower standards of personal hygiene in younger populations.

Abstract

The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted.We used restriction-fragment-length polymorphism (RFLP) analysis to study M. tuberculosis isolates from all patients reported to the tuberculosis registry in San Francisco during 1991 and 1992. These results were interpreted along with clinical, demographic, and epidemiologic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. Risk factors for being in a cluster were analyzed.Of 473 patients studied, 191 appeared to have active tuberculosis as a result of recent infection. Tracing of patients' contacts with the use of conventional methods identified links among only 10 percent of these patients. DNA fingerprinting, however, identified 44 clusters, 20 of which consisted of only 2 persons and the largest of which consisted of 30 persons. In patients under 60 years of age, Hispanic ethnicity (odds ratio, 3.3; P = 0.02), black race (odds ratio, 2.3; P = 0.02), birth in the United States (odds ratio, 5.8; P < 0.001), and a diagnosis of the acquired immunodeficiency syndrome (odds ratio, 1.8; P = 0.04) were independently associated with being in a cluster. Further study of patients in clusters confirmed that poorly compliant patients with infectious tuberculosis have a substantial adverse effect on the control of this disease.Despite an efficient tuberculosis-control program, nearly a third of new cases of tuberculosis in San Francisco are the result of recent infection. Few of these instances of transmission are identified by conventional contact tracing.

Abstract

The objective of this project was to determine the association of Helicobacter pylori infection and serum pepsinogen levels on subsequent risk for gastric adenocarcinoma. This nested case-control study was set in a large health maintenance organization. One hundred thirty-six cases of gastric adenocarcinoma and 136 matched controls without adenocarcinoma from a large cohort that had contributed serum in the 1960's were studied. The presence of IgG against H. pylori had previously been determined by enzyme-linked immunosorbent assay. Serum levels of pepsinogens I and II were ascertained by radioimmunoassay. In a sample of subjects, the presence of antiparietal cell antibodies was determined by immunofluorescent antibody assay (Nichols Laboratory). There were 98 cases of adenocarcinoma of the antrum, body, or fundus (distal cancers) and 30 of the cardia or gastroesophageal junction (proximal cancers). By univariate analysis, H. pylori infection [odds ratio (OR), 3.6; P < 0.001] and serum pepsinogen I < 50 ng/ml (OR = 2.9; P = 0.003) were both associated with development of distal cancer. In multivariate analysis, there was interaction between the two variables; H. pylori in the absence of low pepsinogen I was independently associated with cancer (OR, 2.4; P = 0.04) but low pepsinogen I in the absence of H. pylori infection was not associated with cancer (OR, 0.8; P > 0.5). In combination, however, H. pylori infection and a low pepsinogen I were associated with a marked increase in the risk of developing distal malignancy (OR, 10.0; P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Gastric cancer remains among the leading types of cancer worldwide. There is now convincing evidence linking H. pylori to adenocarcinomas of the gastric antrum, body, and fundus. These tumors are rapidly decreasing in incidence in the United States, whereas cardia tumors, tumors unassociated with H. pylori infection, are on the increase. Although criteria for causality have not been completely fulfilled for H. pylori and adenocarcinoma, there are plausible mechanisms by which chronic inflammation could induce carcinogenesis ("mitosis causes mutagenesis"). Because gastric cancer is unusual in the United States, screening and treatment of H. pylori in the general population are unwarranted. Chemoprevention in high-risk populations, however, could potentially be used to decrease risk for adenocarcinomas distal to the cardia.

Abstract

Paraquat is a bipyridyl herbicide used world-wide. Although accidental and deliberate ingestions of lethal doses have been reported from many countries, no case has ever been described in Mexico. The authors report on 25 cases of Paraquat poisoning in the state of Chiapas, Mexico, that occurred between 1988 and 1990. Eighty percent of the cases were men, and 64% of the cases died. Alcohol intoxication or suicidal intent were factors at the time of Paraquat ingestion in 75% of the cases. The majority of cases had learned to use Paraquat from a friend; none had been instructed by a professional. Eighty percent of cases did not know the dilution for the proper use of the herbicide, and none kept the herbicide in its original container. Attention to the law, redesign of the Paraquat packaging, and educational efforts directed at populations at risk might reduce the occurrence of poisoning in this region.

Abstract

Helicobacter pylori recently was identified as a risk factor for gastric cancer. Its association with preneoplastic conditions of the stomach, however, is undocumented.Gastric biopsy specimens from 245 symptomatic patients were examined for neoplastic and preneoplastic lesions and for gastric H. pylori infection. The sera of 183 subjects were tested by enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori immunoglobulin G.Histologic H. pylori infection, usually accompanied by acute and chronic gastritis, was found in 85.7% of patients. There was a strong association between H. pylori in the tissue and atrophy (relative risk, 15.0; 95% confidence interval, 4.2-56.6), intestinal metaplasia (relative risk, 5.7; 95% confidence interval, 1.9-16.8), and dysplasia or cancer (relative risk, 4.0; 95% confidence interval, 1.1-14.8). The ELISA was 93.2% sensitive and 57.1% specific for histologic infection with a positive predictive value of 96.1%. The overall seroprevalence rate was 86.1%, with no significant difference in rates between patients with cancer precursors and those with normal stomachs.In this high-risk population, precursor lesions for adenocarcinoma were associated universally with H. pylori infection.

Abstract

To identify symptoms and risk factors associated with Helicobacter pylori infection, a cohort of 341 epidemiologists was studied. All subjects had one banked serum (collected between 1969 and 1987) and one recent serum sample (collected in 1988) evaluated for H. pylori immunoglobulin G by enzyme-linked immunosorbent assay; subjects provided information on gastrointestinal symptoms and risk factors for gastritis and peptic ulcer disease. Prevalence of infection decreased from the early 1970s to the present. Eleven subjects (3% of the total cohort) seroconverted during the interval between serum samples, giving a crude conversion rate of 0.49% per person-year (95% confidence interval, 0.3-0.9). Nonreactors on the 1988 serum sample described similar symptoms to reactors. However, subjects who seroconverted in the interval between the two serum samples were more likely than either persistent nonreactors [relative risk (RR), 4.1] or persistent reactors (RR, 3.7) to have experienced upper gastrointestinal symptoms in the interval years. Consumption of caffeinated beverages (RR, 4.6) and residence in the northeastern United States (RR, 5.3) seemed to increase risk for infection. Because pain was similarly common in H. pylori-positive and -negative patients, H. pylori cannot be summarily accepted as the cause of dyspeptic symptoms even when infection is confirmed.

Abstract

Biopsy-proved polymyositis subsequently developed in two patients who were severely poisoned by ciguatera fish toxin. Ciguatera toxin may have several mechanisms of action and may represent more than one toxin. The patients' clinical courses and the unlikelihood of coincidence of contracting both diseases suggested to us a causal relationship. Although we cannot prove this relationship, we suggest a mechanism by which the toxin predisposed the muscle to inflammation.

Abstract

Gastric cancer can be divided into two histologic types: intestinal and diffuse. To determine whether Helicobacter pylori, a bacterium linked with gastritis, was associated with either cancer type, we reviewed histologic sections from stomachs of patients who had undergone gastrectomy for gastric cancer. Of 37 of the sections with evidence of intestinal-type cancer, 33 (89.2%) contained H pylori in noncancerous tissue compared with 7 (31.8%) of 22 of the sections with evidence of diffuse-type cancer (odds ratio = 17.7; P less than .001). This association remained strong when controlled for age, sex, site, and number of sections reviewed. The prevalence of H pylori in intestinal-type gastric cancer far exceeded the prevalence of H pylori in diffuse disease and that described in the normal US population. This finding suggests that H pylori may be a cofactor in development of intestinal-type gastric cancer.

Abstract

During 1988 the number of Shigella dysenteriae type 1 infections reported in the United States increased fivefold. To determine if recent isolates from Mexico were related to those that caused epidemics of dysentery worldwide, Southern hybridization analysis was done with Shiga toxin and ribosomal RNA gene probes. Western hemisphere and Eastern Hemisphere strains differed by the size of a single EcoRI fragment carrying the Shiga toxin genes. Three ribosomal DNA (rDNA) patterns were observed, which correlated with the strain's continental origin for 81 of 83 isolates tested. Together the Shiga toxin and rDNA probe results indicated that recent Mexican isolates were chromosomally similar to earlier Central American isolates and distinct from Asian and African strains. This suggests there has been no significant exchange of organisms between continents in recent decades and that the 1988 outbreak in Mexico was caused by strains present in Central America since at least 1962.

Abstract

An outbreak of a chronic diarrheal syndrome was detected between May and August 1987 in rural Henderson County, Illinois. Seventy-two individuals were affected. Epidemiological studies performed by the Center for Disease Control implicated the water of a local restaurant as the source of the outbreak. Five patients underwent a comprehensive evaluation. Their mean age was 51 years, and they had a mean of 12 watery stools daily (range, 6-40). Detailed microbiological evaluations failed to identify a pathological organism. Stool studies showed a mean stool weight of 392 g/24 h with a normal fat content. Results of all biochemical studies of serum were normal. Chemical analysis of stool water suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients. Electron microscopy of the affected areas revealed no viral particles. After 2 years, all of our patients continued to experience chronic diarrhea. One patient agreed to a follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted after 2 years. We speculate that an infectious process arising from a contaminated water system induced a chronic, secretory diarrhea characterized by multifocal colitis. This histological abnormality may serve as a marker of an infectious, chronic diarrhea.

Abstract

To determine the prevalence of Helicobacter pylori in patients with non-ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease.Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis.H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%.H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism.

Abstract

In 1988, the number of Shigella dysenteriae type 1 (Sd1) infections reported in the USA increased five-fold over the annual mean from the previous decade. 44 (94%) of 47 interviewed patients reported recent travel to Mexico; 33 (75%) of these had been tourists to the Yucatan peninsula. 27 patients who had travelled to Mexico were admitted to hospital, of whom 2 had a haemolytic uraemic syndrome; none died. The antimicrobial resistance pattern and plasmid profile of the Yucatan strain were similar to those of the 1969-72 pandemic strain. Antimicrobial resistances and plasmid profiles were different in sporadic Western hemisphere strains. This is the first outbreak of Sd1 among US tourists and it is the largest known outbreak in the Western hemisphere since the early 1970s. The dominant Sd1 strain is similar to that which caused the catastrophic 1969-72 pandemic. Surveillance and control measures have been instituted in the Yucatan peninsula.

Abstract

A patient receiving continuous ambulatory peritoneal dialysis, and who was known to be seropositive for human immunodeficiency virus but without AIDS or ARC, had peritonitis secondary to Trichosporon beigelii. The patient had been receiving oral antibiotics and had had recurrent bouts of bacterial peritonitis. Infection was cured with removal of the peritoneal catheter and intraperitoneal and intravenous amphotericin B. The course of this episode of Trichosporon beigelii peritonitis was similar to that of peritonitis caused by other yeasts.

Abstract

To determine the cause of an outbreak of chronic diarrhea and to define the clinical profile of the illness.A case series of patients with chronic diarrhea and case-control and cohort studies to determine the vehicle and cause of the illness.Rural Henderson County, Illinois.Seventy-two patients who had onset of chronic diarrheal illness between May and August 1987. Controls were local residents and eating companions who did not have diarrheal illness. A cohort study included 80 truck drivers from a local firm.Nonbloody diarrhea was characterized by extreme frequency (median, 12 stools/d), marked urgency, fecal incontinence, and weight loss (mean, 4.5 kg). The median incubation period was 10 days. Nine patients were hospitalized; none died. Diarrhea persisted in 87% of patients after 6 months. Antimicrobial therapy produced no clinical improvement. No bacterial, mycobacterial, viral, or parasitic agents known to be enteropathogenic were detected in stools or implicated water. Three of five small-bowel biopsies showed mild inflammatory changes. Mild inflammation was also seen in two of nine colonic biopsies. Case-control studies implicated a local restaurant (P = 0.0001, odds ratio = 19) and subsequently the untreated well water served in the restaurant (P = 0.04, odds ratio = 9.3) as the vehicle of transmission.This is the first outbreak of chronic diarrhea linked to drinking untreated water. The causative agent and pathophysiologic mechanism of the illness remain elusive.

Abstract

A study of 84 gastric biopsies taken from 42 adult patients revealed simple techniques for Gram stain and culture for Campylobacter pylori. In an initial study of 18 biopsies, Gram stains prepared from ground, diluted tissue were all negative for curved, gram-negative rods, whereas 13 of these specimens were positive for C. pylori by culture. The Gram stains for the remaining 66 biopsies were prepared by a rinse-imprint technique. In this group, there were 30 Gram stains positive for organisms resembling C. pylori and 32 positive cultures. By Gram-staining two sites, fundus and antrum, the sensitivity of the Gram stain for identifying a positive specimen increased from 91 to 100%. Gram stain may be the preferred technique for rapid diagnosis. When cultured, C. pylori was recovered most often on modified Thayer-Martin medium incubated microaerophilically at 35 degrees C. The presence of antibiotics in modified Thayer-Martin medium limited upper respiratory flora overgrowth, which was often present on nonselective media.